Produção de citocinas por células mononucleares humanas estimuladas por formas amastigotas de Leishmania(Viannia) braziliensis

Detalhes bibliográficos
Autor(a) principal: Gomes, Clayson Moura
Data de Publicação: 2012
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Repositório Institucional da UFG
dARK ID: ark:/38995/0013000001p61
Texto Completo: http://repositorio.bc.ufg.br/tede/handle/tede/3199
Resumo: Introduction: Leishmaniasis is a tropical zoonoses that is endemic, causing different clinical forms including cutaneous, diffuse, disseminated, mucosal and visceral manifestations. The L. (V.) braziliensis is the most common parasite found in cutaneous leishmaniasis in Brazil and is the major agent for the mucosal leishmaniasis. The manifestation of the disease and the clinical forms are dependent on several factors related between the parasite and host. Objective: The aim of this study was to compare the ability of amastigote parasite isolated from patients with cutaneous or mucosal leishmaniasis to stimulate the production of cytokines in peripheral blood mononuclear cells cultures (PBMC) obtained from health donors. Methods: Isolates of patients with cutaneous or mucosal lesion were inoculated in IFNγ knockout mice to obtain amastigotes, which were purifyed by density using Percoll. The PBMCs from healthy individuals were separated by density using Ficoll. The cells were incubated in cultures at different times with amastigotes and then the supernatant were collect to quantify cytokines by ELISA or cells that are used to quantify cytokines using the real time PCR. Results: PBMCs produced higher amounts of IL-1β, IL-6, IL-10 and TGFβ in cultures after stimulation with amastigotes than uninfected controls. When comparing isolates from cutaneous or mucosal disease it was not found differerence regarding to the production of IL-6, IL-10 and TGFβ, but amastigotes from patients with cutaneous leishmaniasis induced more IL-1β than in parasites obtained from mucosal lesion. Production of IFNγ IL17, and TNF was was not detected at different times after stimulation with L. (V.) braziliensis amastigotes. Conclusion: The results suggest that amastigotes of patients with cutaneous leishmaniasis interact with innate immunity cells by inducing the production of proinflammatory or anti-inflammatory and isolated from mucosal lesions induce less IL-1 than parasites obtained from skin lesions. The greatest amount of IL-1 promotes an inflammatory response with migration of cells to the site of infection, so a low xvii production would cause a slower disease and would prejudice an effective acquired response. Thus, the parasite would be able to survive longer in host in a silent way.
id UFG-2_c6189e001c21a38a7264397a85ba029f
oai_identifier_str oai:repositorio.bc.ufg.br:tede/3199
network_acronym_str UFG-2
network_name_str Repositório Institucional da UFG
repository_id_str
spelling Oliveira, Milton Adriano Pelli dehttp://lattes.cnpq.br/2152513705182408Cruvinel, Wilson de MeloPfrimer, Irmtraut Araci HoffmannOliveira, Milton Adriano Pelli dehttp://lattes.cnpq.br/8550177354539916Gomes, Clayson Moura2014-09-26T21:28:37Z2012-02-03GOMES, Clayson Moura. Produção de citocinas por células mononucleares humanas estimuladas por formas amastigotas de Leishmania(Viannia) braziliensis. 2012. 117 f. Dissertação (Mestrado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2012.http://repositorio.bc.ufg.br/tede/handle/tede/3199ark:/38995/0013000001p61Introduction: Leishmaniasis is a tropical zoonoses that is endemic, causing different clinical forms including cutaneous, diffuse, disseminated, mucosal and visceral manifestations. The L. (V.) braziliensis is the most common parasite found in cutaneous leishmaniasis in Brazil and is the major agent for the mucosal leishmaniasis. The manifestation of the disease and the clinical forms are dependent on several factors related between the parasite and host. Objective: The aim of this study was to compare the ability of amastigote parasite isolated from patients with cutaneous or mucosal leishmaniasis to stimulate the production of cytokines in peripheral blood mononuclear cells cultures (PBMC) obtained from health donors. Methods: Isolates of patients with cutaneous or mucosal lesion were inoculated in IFNγ knockout mice to obtain amastigotes, which were purifyed by density using Percoll. The PBMCs from healthy individuals were separated by density using Ficoll. The cells were incubated in cultures at different times with amastigotes and then the supernatant were collect to quantify cytokines by ELISA or cells that are used to quantify cytokines using the real time PCR. Results: PBMCs produced higher amounts of IL-1β, IL-6, IL-10 and TGFβ in cultures after stimulation with amastigotes than uninfected controls. When comparing isolates from cutaneous or mucosal disease it was not found differerence regarding to the production of IL-6, IL-10 and TGFβ, but amastigotes from patients with cutaneous leishmaniasis induced more IL-1β than in parasites obtained from mucosal lesion. Production of IFNγ IL17, and TNF was was not detected at different times after stimulation with L. (V.) braziliensis amastigotes. Conclusion: The results suggest that amastigotes of patients with cutaneous leishmaniasis interact with innate immunity cells by inducing the production of proinflammatory or anti-inflammatory and isolated from mucosal lesions induce less IL-1 than parasites obtained from skin lesions. The greatest amount of IL-1 promotes an inflammatory response with migration of cells to the site of infection, so a low xvii production would cause a slower disease and would prejudice an effective acquired response. Thus, the parasite would be able to survive longer in host in a silent way.Introdução: A leishmaniose é uma zoonose tropical endêmica com diferentes formas clínicas, incluindo as formas cutânea, difusa, disseminada, mucosa e visceral. L. (V.) braziliensis é o parasito mais comumente encontrado na leishmaniose tegumentar no Brasil sendo, o principal agente da leishmaniose mucosa. A manifestação da doença e as formas clínicas existentes são dependentes de diversos fatores relacionados ao parasito e ao hospedeiro. Objetivo: Comparar a habilidade de formas amastigotas isoladas de pacientes com leishmaniose cutânea ou mucosa em estimular a produção de citocinas em células mononucleares do sangue periférico (PBMCs) obtidas de doadores sadios. Métodos: Isolados obtidos de pacientes com lesões cutâneas ou mucosas foram inoculados em camundongos deficientes de IFNγ para obtenção de formas amastigotas, que foram separadas por gradiente de densidade usando o Percoll. As PBMCs de indivíduos sadios foram separadas por gradiente de densidade usando o Ficoll e cultivadas por diferentes tempos com as formas amastigotas. O sobrenadante foi coletado para quantificar as citocinas por ELISA e as células restantes foram lisadas para análise do mRNA para citocinas usando o PCR em tempo real. Resultados: As PBMCs produziram IL-1β, IL-6, IL-10 e TGFβ em culturas após a estimulação com amastigotas. Os isolados de lesões cutâneas produziram quantidades semelhantes de IL-6, IL-10 e TGFβ quando comparados com isolados de lesões mucosas. Formas amastigotas obtidas de pacientes com leishmaniose cutânea induziram uma maior produção de IL-1β do que parasitos obtidos de lesões mucosas. A produção de IFNγ, IL-17, e TNF não foi detectada em todos os tempos avaliados, após a estimulação com amastigotas de L. (V.) braziliensis. Conclusão: Os resultados sugerem que formas amastigotas de pacientes com leishmaniose tegumentar interagem com células da imunidade inata, induzindo a produção de citocinas pró e anti inflamatórias, sendo que isolados oriundos de lesão mucosa induzem menos IL-1 do que parasitos obtidos de lesões cutâneas. A maior quantidade de IL-1 favorece uma resposta inflamatória com a migração de células para xv o local da infecção. Uma baixa produção dessa citocina faria com que a doença fosse mais lenta prejudicando a formação de uma resposta adquirida eficiente. Portanto, o parasito poderia ser capaz de sobreviver por um tempo maior no hospedeiro de uma maneira silenciosa, causando a forma mucosa.Submitted by Erika Demachki (erikademachki@gmail.com) on 2014-09-26T20:15:20Z No. of bitstreams: 2 Clayson Gomes - 2012 - dissertação.pdf: 1729605 bytes, checksum: 48dd1bd05f0e954a3dd14fb20b162e2f (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Approved for entry into archive by Jaqueline Silva (jtas29@gmail.com) on 2014-09-26T21:28:37Z (GMT) No. of bitstreams: 2 Clayson Gomes - 2012 - dissertação.pdf: 1729605 bytes, checksum: 48dd1bd05f0e954a3dd14fb20b162e2f (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5)Made available in DSpace on 2014-09-26T21:28:37Z (GMT). No. of bitstreams: 2 Clayson Gomes - 2012 - dissertação.pdf: 1729605 bytes, checksum: 48dd1bd05f0e954a3dd14fb20b162e2f (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2012-02-03Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESConselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPqapplication/pdfhttp://repositorio.bc.ufg.br/tede/retrieve/8828/Clayson%20Gomes%20-%202012%20-%20disserta%c3%a7%c3%a3o.pdf.jpgporUniversidade Federal de GoiásPrograma de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP)UFGBrasilInstituto de Patologia Tropical e Saúde Pública - IPTSP (RG)Ahmed S, Colmenares M, Soong L, Goldsmith-Pestana K, Munstermann L, Molina R, McMahon-Pratt D 2003. Intradermal infection model for pathogenesis and vaccine studies of murine visceral leishmaniasis. Infect Immun, 71, 401-410. Alborzi A, Pouladfar GR, Fakhar M, Motazedian MH, Hatam GR, Kadivar MR 2008. Isolation of Leishmania tropica from a patient with visceral leishmaniasis and disseminated cutaneous leishmaniasis, southern Iran. Am J Trop Med Hyg, 79, 435-437. Alcolea PJ, Alonso A, Gomez MJ, Moreno I, Dominguez M, Parro V, Larraga V 2010. Transcriptomics throughout the life cycle of Leishmania infantum: high down-regulation rate in the amastigote stage. Int J Parasitol, 40, 1497-1516. Amato VS, Tuon FF, Siqueira AM, Nicodemo AC, Neto VA 2007. Treatment of mucosal leishmaniasis in Latin America: systematic review. Am J Trop Med Hyg, 77, 266-274. Anderson CF, Stumhofer JS, Hunter CA, Sacks D 2009. IL-27 regulates IL-10 and IL-17 from CD4+ cells in nonhealing Leishmania major infection. J Immunol, 183, 4619-4627. Assier E, Boissier MC, Dayer JM 2010. Interleukin-6: from identification of the cytokine to development of targeted treatments. Joint Bone Spine, 77, 532-536. Avila JL, Rojas M, Rieber M 1984. Antibodies to laminin in American cutaneous leishmaniasis. Infect Immun, 43, 402-406. Ávila LR, Gomes CM, Tomé FD, Vinaud MC, Pereira LIA, Duarte FB, Ribeiro-Dias F, Dorta ML, Uliana SR, Oliveira MAP 2012. Leishmania (Viannia) braziliensis isolated 45 from mucosal lesion express more thiol-specific antioxidant protein than parasites isolated from cutaneous lesion. Manuscrito em preparação. Bacellar O, Faria D, Nascimento M, Cardoso TM, Gollob KJ, Dutra WO, Scott P, Carvalho EM 2009. Interleukin 17 production among patients with American cutaneous leishmaniasis. Journal of Infectious Disesases, 200, n. 1, 75-78. Bacellar O, Lessa H, Schriefer A, Machado P, Ribeiro de Jesus A, Dutra WO, Gollob KJ, Carvalho EM 2002. Up-regulation of Th1-type responses in mucosal leishmaniasis patients. Infect Immun, 70, 6734-6740. Bajenoff M, Breart B, Huang AY, Qi H, Cazareth J, Braud VM, Germain RN, Glaichenhaus N 2006. Natural killer cell behavior in lymph nodes revealed by static and real-time imaging. J Exp Med, 203, 619-631. Banuls AL, Hide M, Prugnolle F 2007. Leishmania and the leishmaniases: a parasite genetic update and advances in taxonomy, epidemiology and pathogenicity in humans. Adv Parasitol, 64, 1-109. Barlow JL, McKenzie AN 2011. Nuocytes: expanding the innate cell repertoire in type-2 immunity. J Leukoc Biol. Barral A, Jesus AR, Almeida RP, Carvalho EM, Barral-Netto M, Costa JM, Badaro R, Rocha H, Johnson WD 1987. Evaluation of T-cell subsets in the lesion infiltrates of human cutaneous and mucocutaneous leishmaniasis. Parasite Immunol, 9, 487-497. Bauernfeind F, Ablasser A, Bartok E, Kim S, Schmid-Burgk J, Cavlar T, Hornung V 2011a. Inflammasomes: current understanding and open questions. Cell Mol Life Sci, 68, 765-783. 46 Bauernfeind F, Bartok E, Rieger A, Franchi L, Nunez G, Hornung V 2011b. Cutting edge: reactive oxygen species inhibitors block priming, but not activation, of the NLRP3 inflammasome. J Immunol, 187, 613-617. Beil WJ, Meinardus-Hager G, Neugebauer DC, Sorg C 1992. Differences in the onset of the inflammatory response to cutaneous leishmaniasis in resistant and susceptible mice. J Leukoc Biol, 52, 135-142. Belkaid Y, Piccirillo CA, Mendez S, Shevach EM, Sacks DL 2002. CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature, 420, 502-507. Boaventura VS, Santos CS, Cardoso CR, de Andrade J, Dos Santos WL, Clarencio J, Silva JS, Borges VM, Barral-Netto M, Brodskyn CI, Barral A 2010. Human mucosal leishmaniasis: neutrophils infiltrate areas of tissue damage that express high levels of Th17-related cytokines. Eur J Immunol, 40, 2830-2836. Bogdan C, Rollinghoff M, Diefenbach A 2000. The role of nitric oxide in innate immunity. Immunol Rev, 173, 17-26. Brasil M 2007. Manual de Vigilância da Leishmaniose Tegumentar Americana. 2nd Ed. ed., 2nd Ed. ed., Ministério da Saúde, Brasilia, 182 pp. Brasil MdSd 2006. Atlas de Leishmaniose tegumentar Americana - diagnósticos clínico e diferencial. Ministério da Saúde, Brasilia, 138 pp. Buxbaum LU, Scott P 2005. Interleukin 10- and Fcgamma receptor-deficient mice resolve Leishmania mexicana lesions. Infect Immun, 73, 2101-2108. 47 Buxbaum LU, Uzonna JE, Goldschmidt MH, Scott P 2002. Control of New World cutaneous leishmaniasis is IL-12 independent but STAT4 dependent. Eur J Immunol, 32, 3206-3215. Cabrera M, Shaw MA, Sharples C, Williams H, Castes M, Convit J, Blackwell JM 1995. Polymorphism in tumor necrosis factor genes associated with mucocutaneous leishmaniasis. J Exp Med, 182, 1259-1264. Caceres-Dittmar G, Tapia FJ, Sanchez MA, Yamamura M, Uyemura K, Modlin RL, Bloom BR, Convit J 1993. Determination of the cytokine profile in American cutaneous leishmaniasis using the polymerase chain reaction. Clin Exp Immunol, 91, 500-505. Campanelli AP, Roselino AM, Cavassani KA, Pereira MS, Mortara RA, Brodskyn CI, Goncalves HS, Belkaid Y, Barral-Netto M, Barral A, Silva JS 2006. CD4+CD25+ T cells in skin lesions of patients with cutaneous leishmaniasis exhibit phenotypic and functional characteristics of natural regulatory T cells. J Infect Dis, 193, 1313-1322. Carvalho EM, Barral A, Costa JM, Bittencourt A, Marsden P 1994. Clinical and immunopathological aspects of disseminated cutaneous leishmaniasis. Acta Trop, 56, 315-325. Carvalho EM, Correia Filho D, Bacellar O, Almeida RP, Lessa H, Rocha H 1995. Characterization of the immune response in subjects with self-healing cutaneous leishmaniasis. Am J Trop Med Hyg, 53, 273-277. Cassatella MA 1995. The production of cytokines by polymorphonuclear neutrophils. Immunol Today, 16, 21-26. Castellucci L, Menezes E, Oliveira J, Magalhaes A, Guimaraes LH, Lessa M, Ribeiro S, Reale J, Noronha EF, Wilson ME, Duggal P, Beaty TH, Jeronimo S, Jamieson SE, Bales A, Blackwell JM, de Jesus AR, Carvalho EM 2006. IL6 -174 G/C promoter 48 polymorphism influences susceptibility to mucosal but not localized cutaneous leishmaniasis in Brazil. J Infect Dis, 194, 519-527. Chen M, Wang H, Chen W, Meng G 2011. Regulation of adaptive immunity by the NLRP3 inflammasome. Int Immunopharmacol, 11, 549-554. Clem A 2010. A current perspective on leishmaniasis. J Glob Infect Dis, 2, 124-126. Colotti G, Ilari A 2010. Polyamine metabolism in Leishmania: from arginine to trypanothione. Amino Acids, 40, 269-285. Convit JU, M. 1993. Antigen-specific immunodeficiency and its relation to the spectrum of American cutaneous leishmaniasis. Biol Res, 26, 159-166. Costa DL, Carregaro V, Lima-Junior DS, Silva NM, Milanezi CM, Cardoso CR, Giudice A, de Jesus AR, Carvalho EM, Almeida RP, Silva JS 2011. BALB/c mice infected with antimony treatment refractory isolate of Leishmania braziliensis present severe lesions due to IL-4 production. PLoS Negl Trop Dis, 5, e965. Costa JM, Vale KC, Cecilio IN, Osaki NK, Netto EM, Tada MS, Franca F, Barreto MC, Marsden PD 1987. Psychosocial and stigmatizing aspects of mucocutaneous leishmaniasis. Rev Soc Bras Med Trop, 20, 77-81. Cruvinel WM, Mesquita D, Jr., Araujo JA, Catelan TT, de Souza AW, da Silva NP, Andrade LE 2010. Immune system - part I. Fundamentals of innate immunity with emphasis on molecular and cellular mechanisms of inflammatory response. Rev Bras Reumatol, 50, 434-461. 49 Cuervo P, Cupolillo E, Nehme N, Hernandez V, Saravia N, Fernandes O 2004. Leishmania (Viannia): genetic analysis of cutaneous and mucosal strains isolated from the same patient. Exp Parasitol, 108, 59-66. Cupolillo E, Brahim LR, Toaldo CB, de Oliveira-Neto MP, de Brito ME, Falqueto A, de Farias Naiff M, Grimaldi G, Jr. 2003. Genetic polymorphism and molecular epidemiology of Leishmania (Viannia) braziliensis from different hosts and geographic areas in Brazil. J Clin Microbiol, 41, 3126-3132. Daneshbod Y, Oryan A, Davarmanesh M, Shirian S, Negahban S, Aledavood A, Davarpanah MA, Soleimanpoor H, Daneshbod K 2011. Clinical, histopathologic, and cytologic diagnosis of mucosal leishmaniasis and literature review. Arch Pathol Lab Med, 135, 478-482. Das J, Ren G, Zhang L, Roberts AI, Zhao X, Bothwell AL, Van Kaer L, Shi Y, Das G 2009. Transforming growth factor beta is dispensable for the molecular orchestration of Th17 cell differentiation. J Exp Med, 206, 2407-2416. David CV, Craft N 2009. Cutaneous and mucocutaneous leishmaniasis. Dermatol Ther, 22, 491-502. de Baey A, Mende I, Riethmueller G, Baeuerle PA 2001. Phenotype and function of human dendritic cells derived from M-DC8(+) monocytes. Eur J Immunol, 31, 1646-1655. de Magalhaes AV, Moraes MA, Raick AN, Llanos-Cuentas A, Costa JM, Cuba CC, Marsden PD 1986. Histopathology of cutaneous leishmaniasis caused by Leishmania braziliensis braziliensis . 4.Histopathological classification. Rev Inst Med Trop Sao Paulo, 28, 421-430. 50 de Moura TR, Novais FO, Oliveira F, Clarencio J, Noronha A, Barral A, Brodskyn C, de Oliveira CI 2005. Toward a novel experimental model of infection to study American cutaneous leishmaniasis caused by Leishmania braziliensis. Infect Immun, 73, 5827-5834. de Souza-Neto SM, Carneiro CM, Vieira LQ, Afonso LC 2004. Leishmania braziliensis: partial control of experimental infection by interleukin-12 p40 deficient mice. Mem Inst Oswaldo Cruz, 99, 289-294. de Souza Carmo EV, Katz S, Barbieri CL 2010. Neutrophils reduce the parasite burden in Leishmania (Leishmania) amazonensis-infected macrophages. PLoS One, 5, e13815. DeKrey GK, Lima HC, Titus RG 1998. Analysis of the immune responses of mice to infection with Leishmania braziliensis. Infect Immun, 66, 827-829. Derouin F 2007. Parasitic infection in immunocompromised patients. Rev Prat, 57, 167-173. Diaz NL, Arvelaez FA, Zerpa O, Tapia FJ 2006. Inducible nitric oxide synthase and cytokine pattern in lesions of patients with American cutaneous leishmaniasis. Clin Exp Dermatol, 31, 114-117. Dinarello CA 2011. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood, 117, 3720-3732. Dominguez M, Moreno I, Aizpurua C, Torano A 2003. Early mechanisms of Leishmania infection in human blood. Microbes Infect, 5, 507-513. 51 Doyle MA, MacRae JI, De Souza DP, Saunders EC, McConville MJ, Likic VA 2009. LeishCyc: a biochemical pathways database for Leishmania major. BMC Syst Biol, 3, 57. Espinosa V, Rivera A 2011. Cytokines and the regulation of fungus-specific CD4 T cell differentiation. Cytokine. Esterre P, Dedet JP, Frenay C, Chevallier M, Grimaud JA 1992. Cell populations in the lesion of human cutaneous leishmaniasis: a light microscopical, immunohistochemical and ultrastructural study. Virchows Arch A Pathol Anat Histopathol, 421, 239-247. Faria DR, Gollob KJ, Barbosa J, Jr., Schriefer A, Machado PR, Lessa H, Carvalho LP, Romano-Silva MA, de Jesus AR, Carvalho EM, Dutra WO 2005. Decreased in situ expression of interleukin-10 receptor is correlated with the exacerbated inflammatory and cytotoxic responses observed in mucosal leishmaniasis. Infect Immun, 73, 7853-7859. Filardy AA, Pires DR, DosReis GA 2011. Macrophages and neutrophils cooperate in immune responses to Leishmania infection. Cell Mol Life Sci, 68, 1863-1870. Ghaemi-Oskouie F, Shi Y 2011. The role of uric acid as an endogenous danger signal in immunity and inflammation. Curr Rheumatol Rep, 13, 160-166. Ghoreschi K, Laurence A, Yang XP, Tato CM, McGeachy MJ, Konkel JE, Ramos HL, Wei L, Davidson TS, Bouladoux N, Grainger JR, Chen Q, Kanno Y, Watford WT, Sun HW, Eberl G, Shevach EM, Belkaid Y, Cua DJ, Chen W, O'Shea JJ 2010. Generation of pathogenic T(H)17 cells in the absence of TGF-beta signalling. Nature, 467, 967-971. Giudice A, Camada I, Leopoldo PT, Pereira JM, Riley LW, Wilson ME, Ho JL, de Jesus AR, Carvalho EM, Almeida RP 2007. Resistance of Leishmania (Leishmania) 52 amazonensis and Leishmania (Viannia) braziliensis to nitric oxide correlates with disease severity in Tegumentary Leishmaniasis. BMC Infect Dis, 7, 7. Gomes-Silva A, de Cassia Bittar R, Dos Santos Nogueira R, Amato VS, da Silva Mattos M, Oliveira-Neto MP, Coutinho SG, Da-Cruz AM 2007. Can interferon-gamma and interleukin-10 balance be associated with severity of human Leishmania (Viannia) braziliensis infection? Clin Exp Immunol, 149, 440-444. Gordon S 2003. Alternative activation of macrophages. Nat Rev Immunol, 3, 23-35. Goto H, Lindoso JA 2010. Current diagnosis and treatment of cutaneous and mucocutaneous leishmaniasis. Expert Rev Anti Infect Ther, 8, 419-433. Grevelink SA, Lerner EA 1996. Leishmaniasis. J Am Acad Dermatol, 34, 257-272. Guerra JA, Prestes SR, Silveira H, Coelho LI, Gama P, Moura A, Amato V, Barbosa MG, Ferreira LC 2011. Mucosal Leishmaniasis caused by Leishmania (Viannia) braziliensis and Leishmania (Viannia) guyanensis in the Brazilian Amazon. PLoS Negl Trop Dis, 5, e980. Guimaraes-Costa AB, Nascimento MT, Froment GS, Soares RP, Morgado FN, Conceicao-Silva F, Saraiva EM 2009. Leishmania amazonensis promastigotes induce and are killed by neutrophil extracellular traps. Proc Natl Acad Sci U S A, 106, 6748-6753. Gutierrez Y, Salinas GH, Palma G, Valderrama LB, Santrich CV, Saravia NG 1991. Correlation between histopathology, immune response, clinical presentation, and evolution in Leishmania braziliensis infection. Am J Trop Med Hyg, 45, 281-289. 53 Hawrylowicz CM 2005. Regulatory T cells and IL-10 in allergic inflammation. J Exp Med, 202, 1459-1463. Heinzel FP, Sadick MD, Holaday BJ, Coffman RL, Locksley RM 1989. Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J Exp Med, 169, 59-72. Hernandez-Ruiz J, Salaiza-Suazo N, Carrada G, Escoto S, Ruiz-Remigio A, Rosenstein Y, Zentella A, Becker I 2010. CD8 cells of patients with diffuse cutaneous leishmaniasis display functional exhaustion: the latter is reversed, in vitro, by TLR2 agonists. PLoS Negl Trop Dis, 4, e871. Herwaldt BL 1999. Leishmaniasis. Lancet, 354, 1191-1199. Hofmann SR, Ettinger R, Zhou YJ, Gadina M, Lipsky P, Siegel R, Candotti F, O'Shea JJ 2002. Cytokines and their role in lymphoid development, differentiation and homeostasis. Curr Opin Allergy Clin Immunol, 2, 495-506. Jones TC, Johnson WD, Jr., Barretto AC, Lago E, Badaro R, Cerf B, Reed SG, Netto EM, Tada MS, Franca TF, et al. 1987. Epidemiology of American cutaneous leishmaniasis due to Leishmania braziliensis braziliensis. J Infect Dis, 156, 73-83. Kautz-Neu K, Kostka SL, Dinges S, Iwakura Y, Udey MC, von Stebut E 2010. IL-1 signalling is dispensable for protective immunity in Leishmania-resistant mice. Exp Dermatol, 20, 76-78. Kimblin N, Peters N, Debrabant A, Secundino N, Egen J, Lawyer P, Fay MP, Kamhawi S, Sacks D 2008. Quantification of the infectious dose of Leishmania major transmitted to the skin by single sand flies. Proc Natl Acad Sci U S A, 105, 10125-10130. 54 Kimura A, Kishimoto T 2011. Th17 cells in inflammation. Int Immunopharmacol, 11, 319-322. Kostka SL, Knop J, Konur A, Udey MC, von Stebut E 2006. Distinct roles for IL-1 receptor type I signaling in early versus established Leishmania major infections. J Invest Dermatol, 126, 1582-1589. Kropf P, Fuentes JM, Fahnrich E, Arpa L, Herath S, Weber V, Soler G, Celada A, Modolell M, Muller I 2005. Arginase and polyamine synthesis are key factors in the regulation of experimental leishmaniasis in vivo. FASEB J, 19, 1000-1002. Kryczek I, Wei S, Vatan L, Escara-Wilke J, Szeliga W, Keller ET, Zou W 2007. Cutting edge: opposite effects of IL-1 and IL-2 on the regulation of IL-17+ T cell pool IL-1 subverts IL-2-mediated suppression. J Immunol, 179, 1423-1426. Lachmann HJ, Quartier P, So A, Hawkins PN 2011. The emerging role of interleukin-1beta in autoinflammatory diseases. Arthritis Rheum, 63, 314-324. Lane T, Lachmann HJ 2011. The Emerging Role of Interleukin-1beta in Autoinflammatory Diseases. Curr Allergy Asthma Rep. Lang T, Goyard S, Lebastard M, Milon G 2005. Bioluminescent Leishmania expressing luciferase for rapid and high throughput screening of drugs acting on amastigote-harbouring macrophages and for quantitative real-time monitoring of parasitism features in living mice. Cell Microbiol, 7, 383-392. Lei SM, Romine NM, Beetham JK 2010. Population changes in Leishmania chagasi promastigote developmental stages due to serial passage. J Parasitol, 96, 1134-1138. 55 Leite PM, Gomes RS, Figueiredo AB, Fietto JLR, Melo MN, Ribeiro-Dias F, Oliveira MAP, Rabello A, Afonso LCC 2012. Ecto-nucleotidasic activity, infectivity and clinical outcome in Leishmania braziliensis isolates. Artigo submetido para publicação. Liddiard K, Rosas M, Davies LC, Jones SA, Taylor PR 2011. Macrophage heterogeneity and acute inflammation. Eur J Immunol, 41, 2503-2508. Liese J, Schleicher U, Bogdan C 2008. The innate immune response against Leishmania parasites. Immunobiology, 213, 377-387. Liew FY, O'Donnell CA 1993. Immunology of leishmaniasis. Adv Parasitol, 32, 161-259. Maioli TU, Takane E, Arantes RM, Fietto JL, Afonso LC 2004. Immune response induced by New World Leishmania species in C57BL/6 mice. Parasitol Res, 94, 207-212. Maizels RM, Pearce EJ, Artis D, Yazdanbakhsh M, Wynn TA 2009. Regulation of pathogenesis and immunity in helminth infections. J Exp Med, 206, 2059-2066. Maretti-Mira AC, de Pinho Rodrigues KM, de Oliveira-Neto MP, Pirmez C, Craft N 2011. MMP-9 activity is induced by Leishmania braziliensis infection and correlates with mucosal leishmaniasis. Acta Trop. Marsden PD 1994. Mucosal leishmaniasis due to Leishmania (Viannia) braziliensis L(V)b in Três Braços, Bahia-Brazil. Rev Soc Bras Med Trop, 27, 93-101. Martinez-Arends A, Tapia FJ, Caceres-Dittmar G, Mosca W, Valecillos L, Convit J 1991. Immunocytochemical characterization of immune cells in lesions of American cutaneous leishmaniasis using novel T cell markers. Acta Trop, 49, 271-280. 56 McMahon-Pratt D, Alexander J 2004. Does the Leishmania major paradigm of pathogenesis and protection hold for New World cutaneous leishmaniases or the visceral disease? Immunol Rev, 201, 206-224. Meddeb-Garnaoui A, Zrelli H, Dellagi K 2009. Effects of tropism and virulence of Leishmania parasites on cytokine production by infected human monocytes. Clin Exp Immunol, 155, 199-206. Mendez S, Reckling SK, Piccirillo CA, Sacks D, Belkaid Y 2004. Role for CD4(+) CD25(+) regulatory T cells in reactivation of persistent leishmaniasis and control of concomitant immunity. J Exp Med, 200, 201-210. Mitropoulos P, Konidas P, Durkin-Konidas M 2011. New World cutaneous leishmaniasis: updated review of current and future diagnosis and treatment. J Am Acad Dermatol, 63, 309-322. Modolell M, Choi BS, Ryan RO, Hancock M, Titus RG, Abebe T, Hailu A, Muller I, Rogers ME, Bangham CR, Munder M, Kropf P 2009. Local suppression of T cell responses by arginase-induced L-arginine depletion in nonhealing leishmaniasis. PLoS Negl Trop Dis, 3, e480. Mougneau E, Bihl F, Glaichenhaus N 2011. Cell biology and immunology of Leishmania. Immunol Rev, 240, 286-296. Mucida D, Cheroutre H 2007. TGFbeta and retinoic acid intersect in immune-regulation. Cell Adh Migr, 1, 142-144. Mukbel RM, Patten C, Jr., Gibson K, Ghosh M, Petersen C, Jones DE 2007. Macrophage killing of Leishmania amazonensis amastigotes requires both nitric oxide and superoxide. Am J Trop Med Hyg, 76, 669-675. 57 Murray HW 2008. Accelerated control of visceral Leishmania donovani infection in interleukin-6-deficient mice. Infect Immun, 76, 4088-4091. Novoa R, Bacellar O, Nascimento M, Cardoso TM, Ramasawmy R, Oliveira WN, Schriefer A, Carvalho EM 2010. IL-17 and Regulatory Cytokines (IL-10 and IL-27) in L. braziliensis Infection. Parasite Immunol, 33, 132-136. Nylen S, Gautam S 2010. Immunological perspectives of leishmaniasis. J Glob Infect Dis, 2, 135-146. Oliveira F, Bafica A, Rosato AB, Favali CB, Costa JM, Cafe V, Barral-Netto M, Barral A 2011. Lesion Size Correlates with Leishmania Antigen-Stimulated TNF-Levels in Human Cutaneous Leishmaniasis. Am J Trop Med Hyg, 85, 70-73. Oliveira MA, Pires Ada S, de Bastos RP, Lima GM, Pinto SA, Pereira LI, Pereira AJ, Abrahamsohn Ide A, Dorta ML, Ribeiro-Dias F 2010. Leishmania spp. parasite isolation through inoculation of patient biopsy macerates in interferon gamma knockout mice. Rev Inst Med Trop Sao Paulo, 52, 83-88. Pappu BP, Angkasekwinai P, Dong C 2008. Regulatory mechanisms of helper T cell differentiation: new lessons learned from interleukin 17 family cytokines. Pharmacol Ther, 117, 374-384. Passos STS, J. S.; O'hara, A. C.; Sehy, D.; Stumhofer, J. S.; Hunter, C. A. 2010. IL-6 promotes NK cell production of IL-17 during toxoplasmosis. Journal of Immunology, 184, 1776-1783. Passos VM, Lasmar EB, Gontijo CM, Fernandes O, Degrave W 1996. Natural infection of a domestic cat (Felis domesticus) with Leishmania (Viannia) in the metropolitan region of Belo Horizonte, State of Minas Gerais, Brazil. Mem Inst Oswaldo Cruz, 91, 19-20. 58 Pereira CG, Silva AL, de Castilhos P, Mastrantonio EC, Souza RA, Romao RP, Rezende RJ, Pena JD, Beletti ME, Souza MA 2009a. Different isolates from Leishmania braziliensis complex induce distinct histopathological features in a murine model of infection. Vet Parasitol, 165, 231-240. Pereira LI, Dorta ML, Pereira AJ, Bastos RP, Oliveira MA, Pinto SA, Galdino H, Jr., Mayrink W, Barcelos W, Toledo VP, Lima GM, Ribeiro-Dias F 2009b. Increase of NK cells and proinflammatory monocytes are associated with the clinical improvement of diffuse cutaneous leishmaniasis after immunochemotherapy with BCG/Leishmania antigens. Am J Trop Med Hyg, 81, 378-383. Peters N, Sacks D 2006. Immune privilege in sites of chronic infection: Leishmania and regulatory T cells. Immunol Rev, 213, 159-179. Phelan SA 1999. AOP2 (antioxidant protein 2): structure and function of a unique thiol-specific antioxidant. Antioxid Redox Signal, 1, 571-584. Pirmez C, Cooper C, Paes-Oliveira M, Schubach A, Torigian VK, Modlin RL 1990. Immunologic responsiveness in American cutaneous leishmaniasis lesions. J Immunol, 145, 3100-3104. Pirmez C, Yamamura M, Uyemura K, Paes-Oliveira M, Conceicao-Silva F, Modlin RL 1993. Cytokine patterns in the pathogenesis of human leishmaniasis. J Clin Invest, 91, 1390-1395. Pitta MG, Romano A, Cabantous S, Henri S, Hammad A, Kouriba B, Argiro L, el Kheir M, Bucheton B, Mary C, El-Safi SH, Dessein A 2009. IL-17 and IL-22 are associated with protection against human kala azar caused by Leishmania donovani. J Clin Invest, 119, 2379-2387. 59 Pluddemann A, Mukhopadhyay S, Gordon S 2011. Innate immunity to intracellular pathogens: macrophage receptors and responses to microbial entry. Immunol Rev, 240, 11-24. Reynolds JM, Angkasekwinai P, Dong C 2010. IL-17 family member cytokines: regulation and function in innate immunity. Cytokine Growth Factor Rev, 21, 413-423. Rocha FJ, Schleicher U, Mattner J, Alber G, Bogdan C 2007. Cytokines, signaling pathways, and effector molecules required for the control of Leishmania (Viannia) braziliensis in mice. Infect Immun, 75, 3823-3832. Roshick C, Wood H, Caldwell HD, McClarty G 2006. Comparison of gamma interferon-mediated antichlamydial defense mechanisms in human and mouse cells. Infect Immun, 74, 225-238. Sabat R, Grutz G, Warszawska K, Kirsch S, Witte E, Wolk K, Geginat J 2010. Biology of interleukin-10. Cytokine Growth Factor Rev, 21, 331-344. Sacks D, Anderson C 2004. Re-examination of the immunosuppressive mechanisms mediating non-cure of Leishmania infection in mice. Immunol Rev, 201, 225-238. Salay G, Dorta ML, Santos NM, Mortara RA, Brodskyn C, Oliveira CI, Barbieri CL, Rodrigues MM 2007. Testing of four Leishmania vaccine candidates in a mouse model of infection with Leishmania (Viannia) braziliensis, the main causative agent of cutaneous leishmaniasis in the New World. Clin Vaccine Immunol, 14, 1173-1181. Salhi A, Rodrigues V, Jr., Santoro F, Dessein H, Romano A, Castellano LR, Sertorio M, Rafati S, Chevillard C, Prata A, Alcais A, Argiro L, Dessein A 2008. Immunological and genetic evidence for a crucial role of IL-10 in cutaneous lesions in humans infected with Leishmania braziliensis. J Immunol, 180, 6139-6148. 60 Sanchez JL, Diniega BM, Small JW, Miller RN, Andujar JM, Weina PJ, Lawyer PG, Ballou WR, Lovelace JK 1992. Epidemiologic investigation of an outbreak of cutaneous leishmaniasis in a defined geographic focus of transmission. Am J Trop Med Hyg, 47, 47-54. Santarlasci V, Maggi L, Capone M, Frosali F, Querci V, De Palma R, Liotta F, Cosmi L, Maggi E, Romagnani S, Annunziato F 2009. TGF-beta indirectly favors the development of human Th17 cells by inhibiting Th1 cells. Eur J Immunol, 39, 207-215. Saravia NG, Weigle K, Segura I, Giannini SH, Pacheco R, Labrada LA, Goncalves A 1990. Recurrent lesions in human Leishmania braziliensis infection--reactivation or reinfection? Lancet, 336, 398-402. Sartori A, Oliveira MA, Scott P, Trinchieri G 1997. Metacyclogenesis modulates the ability of Leishmania promastigotes to induce IL-12 production in human mononuclear cells. J Immunol, 159, 2849-2857. Scharton-Kersten T, Nakajima H, Yap G, Sher A, Leonard WJ 1998. Infection of mice lacking the common cytokine receptor gamma-chain (gamma(c)) reveals an unexpected role for CD4+ T lymphocytes in early IFN-gamma-dependent resistance to Toxoplasma gondii. J Immunol, 160, 2565-2569. Scharton TM, Scott P 1993. Natural killer cells are a source of interferon gamma that drives differentiation of CD4+ T cell subsets and induces early resistance to Leishmania major in mice. J Exp Med, 178, 567-577. Scott PA, D.; Uzonna, J.; Zaph, C. 2004. The development of effector and memory T cells in cutaneous leishmaniasis: the implications for vaccine development. Immunological Reviews, 201, 318-338. 61 Sethuraman GV, K. Sharma 2008. Indian mucosal leishmaniasis due to Leishmania donovani infection. N Engl J Med, 358, 313-315. Shakya N, Sane SA, Vishwakarma P, Bajpai P, Gupta S 2011. Improved treatment of visceral leishmaniasis (kala-azar) by using combination of ketoconazole, miltefosine with an immunomodulator-Picroliv. Acta Trop. Silveira FT, Lainson R, Corbett CE 2004. Clinical and immunopathological spectrum of American cutaneous leishmaniasis with special reference to the disease in Amazonian Brazil: a review. Mem Inst Oswaldo Cruz, 99, 239-251. Silveira FT, Laison R, Corbett CE 2005. Further observations on clinical, histopathological, and immunological features of borderline disseminated cutaneous leishmaniasis caused by Leishmania (Leishmania) amazonensis. Mem Inst Oswaldo Cruz, 100, 525-534. Silveira FT, Lainson R, De Castro Gomes CM, Laurenti MD, Corbett CE 2009. Immunopathogenic competences of Leishmania (V.) braziliensis and L. (L.) amazonensis in American cutaneous leishmaniasis. Parasite Immunol, 31, 423-431. Singh S, Sharma U, Mishra J 2011. Post-kala-azar dermal leishmaniasis: recent developments. Int J Dermatol, 50, 1099-1108. Skeiky YA, Guderian JA, Benson DR, Bacelar O, Carvalho EM, Kubin M, Badaro R, Trinchieri G, Reed SG 1995. A recombinant Leishmania antigen that stimulates human peripheral blood mononuclear cells to express a Th1-type cytokine profile and to produce interleukin 12. J Exp Med, 181, 1527-1537. Souza AS, Giudice A, Pereira JM, Guimaraes LH, de Jesus AR, de Moura TR, Wilson ME, Carvalho EM, Almeida RP 2010. Resistance of Leishmania (Viannia) braziliensis 62 to nitric oxide: correlation with antimony therapy and TNF-alpha production. BMC Infect Dis, 10, 209. Strutt TM, McKinstry KK, Swain SL 2011. Control of innate immunity by memory CD4 T cells. Adv Exp Med Biol, 780, 57-68. Tabatabaie FGf, FF. Dalimi,A. Sharifi, Z. Zavaran Hoseini, A. 2007. Cloning and Sequencing of Leishmania major Thiol-Specific-Antioxidant Antigen (TSA) Gene. Iranian Journal of Parasitology, 2, nº 4. Tandon A, Tovey JC, Sharma A, Gupta R, Mohan RR 2010. Role of transforming growth factor Beta in corneal function, biology and pathology. Curr Mol Med, 10, 565-578. Tansey MG, Szymkowski DE 2009. The TNF superfamily in 2009: new pathways, new indications, and new drugs. Drug Discov Today, 14, 1082-1088. Tapia FJ, Caceres-Dittmar G, Sanchez MA 1994. Inadequate epidermal homing leads to tissue damage in human cutaneous leishmaniasis. Immunol Today, 15, 160-165. Trinchieri G 2003. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol, 3, 133-146. Underhill DM, Ozinsky A 2002. Phagocytosis of microbes: complexity in action. Annu Rev Immunol, 20, 825-852. Van Assche T, Deschacht M, da Luz RA, Maes L, Cos P 2011. Leishmania-macrophage interactions: Insights into the redox biology. Free Radic Biol Med, 51, 337-351. 63 Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B 2006. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity, 24, 179-189. Vendrame CM, Souza LD, Carvalho MD, Salgado K, Carvalho EM, Goto H 2010. Insulin-like growth factor-I induced and constitutive arginase activity differs among isolates of Leishmania derived from patients with diverse clinical forms of Leishmania braziliensis infection. Trans R Soc Trop Med Hyg, 104, 566-568. Volpini AC, Passos VM, Oliveira GC, Romanha AJ 2004. PCR-RFLP to identify Leishmania (Viannia) braziliensis and L. (Leishmania) amazonensis causing American cutaneous leishmaniasis. Acta Trop, 90, 31-37. Von Stebut EE, J. M.; Belkaid, Y.; Kostka, S. L.; Molle, K.; Knop, J.; Sunderkotter, C.; Udey, M. C. I. 2003. Interleukin 1 alpha promotes Th1 differentiation and inhibits disease progression in Leishmania major-susceptible BALB/c mice. Journal of Experimental Medicine, 198, 191-199. Voronov E, Dotan S, Gayvoronsky L, White RM, Cohen I, Krelin Y, Benchetrit F, Elkabets M, Huszar M, El-On J, Apte RN 2010. IL-1-induced inflammation promotes development of leishmaniasis in susceptible BALB/c mice. Int Immunol, 22, 245-257. Watford WT, Moriguchi M, Morinobu A, O'Shea JJ 2003. The biology of IL-12: coordinating innate and adaptive immune responses. Cytokine Growth Factor Rev, 14, 361-368. Weigle K, Saravia NG 1996. Natural history, clinical evolution, and the host-parasite interaction in New World cutaneous Leishmaniasis. Clin Dermatol, 14, 433-450. 64 Wojtkowiak A 2007. The investigations of the role of toll-like receptors (TLR) in host response to parasitic infection on the current background regarding TLR in mammals and the model nematode Caenorhabditis elegans. Wiad Parazytol, 53, 203-211. Xin L, Li Y, Soong L 2007. Role of interleukin-1 beta in activating the CD11c (high) CD45RB- dendritic cell subset and priming Leishmania amazonensis-specific CD4+ T cells in vitro and in vivo. Infect Immun, 75, 5018-5026.6085308344741430434600600600600600-776901144456455628859899191883767476142075167498588264571-2555911436985713659http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessLeishmania (Viannia) braziliensisLeishmaniose cutâneaLeishmaniose mucosaCélulas mononuclearesCitocinaHumanLeishmaniasisCIENCIAS BIOLOGICAS::IMUNOLOGIAProdução de citocinas por células mononucleares humanas estimuladas por formas amastigotas de Leishmania(Viannia) braziliensisCytokine production by human mononuclear cells estimulated by amastigotes of Leishmania(Viannia) braziliensisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisreponame:Repositório Institucional da UFGinstname:Universidade Federal de Goiás (UFG)instacron:UFGLICENSElicense.txtlicense.txttext/plain; charset=utf-82165http://repositorio.bc.ufg.br/tede/bitstreams/a21b9619-d33c-49e5-b238-9796c74e20ee/downloadbd3efa91386c1718a7f26a329fdcb468MD51CC-LICENSElicense_urllicense_urltext/plain; charset=utf-849http://repositorio.bc.ufg.br/tede/bitstreams/485cb06b-3667-45a5-85f1-993c70702a91/download4afdbb8c545fd630ea7db775da747b2fMD52license_textlicense_texttext/html; charset=utf-822302http://repositorio.bc.ufg.br/tede/bitstreams/3c2651b0-2e03-41f1-93bf-11bbb196375f/download1e0094e9d8adcf16b18effef4ce7ed83MD53license_rdflicense_rdfapplication/rdf+xml; charset=utf-823148http://repositorio.bc.ufg.br/tede/bitstreams/b759f615-c8fb-4828-9892-13b6d89c53a2/download9da0b6dfac957114c6a7714714b86306MD54ORIGINALClayson Gomes - 2012 - dissertação.pdfClayson Gomes - 2012 - dissertação.pdfDissertaçãoapplication/pdf1729605http://repositorio.bc.ufg.br/tede/bitstreams/d294c9f5-e50c-4b74-9eaa-0dd553d24122/download48dd1bd05f0e954a3dd14fb20b162e2fMD55TEXTClayson Gomes - 2012 - dissertação.pdf.txtClayson Gomes - 2012 - dissertação.pdf.txtExtracted Texttext/plain180934http://repositorio.bc.ufg.br/tede/bitstreams/acea2c49-6f9e-4e29-8e77-2e1f1b1dcc5c/downloadb89fdef7cd297855769f9f44eebb6c5bMD56THUMBNAILClayson Gomes - 2012 - dissertação.pdf.jpgClayson Gomes - 2012 - dissertação.pdf.jpgGenerated Thumbnailimage/jpeg2374http://repositorio.bc.ufg.br/tede/bitstreams/9de6d0ec-6079-4c01-a1e6-82ed5a2ec5f8/download632a8af04dc05b92e51373c484153bb6MD57tede/31992014-09-27 03:03:21.956http://creativecommons.org/licenses/by-nc-nd/4.0/Acesso Abertoopen.accessoai:repositorio.bc.ufg.br:tede/3199http://repositorio.bc.ufg.br/tedeRepositório InstitucionalPUBhttp://repositorio.bc.ufg.br/oai/requesttasesdissertacoes.bc@ufg.bropendoar:2014-09-27T06:03:21Repositório Institucional da UFG - Universidade Federal de Goiás (UFG)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
dc.title.por.fl_str_mv Produção de citocinas por células mononucleares humanas estimuladas por formas amastigotas de Leishmania(Viannia) braziliensis
dc.title.alternative.eng.fl_str_mv Cytokine production by human mononuclear cells estimulated by amastigotes of Leishmania(Viannia) braziliensis
title Produção de citocinas por células mononucleares humanas estimuladas por formas amastigotas de Leishmania(Viannia) braziliensis
spellingShingle Produção de citocinas por células mononucleares humanas estimuladas por formas amastigotas de Leishmania(Viannia) braziliensis
Gomes, Clayson Moura
Leishmania (Viannia) braziliensis
Leishmaniose cutânea
Leishmaniose mucosa
Células mononucleares
Citocina
Human
Leishmaniasis
CIENCIAS BIOLOGICAS::IMUNOLOGIA
title_short Produção de citocinas por células mononucleares humanas estimuladas por formas amastigotas de Leishmania(Viannia) braziliensis
title_full Produção de citocinas por células mononucleares humanas estimuladas por formas amastigotas de Leishmania(Viannia) braziliensis
title_fullStr Produção de citocinas por células mononucleares humanas estimuladas por formas amastigotas de Leishmania(Viannia) braziliensis
title_full_unstemmed Produção de citocinas por células mononucleares humanas estimuladas por formas amastigotas de Leishmania(Viannia) braziliensis
title_sort Produção de citocinas por células mononucleares humanas estimuladas por formas amastigotas de Leishmania(Viannia) braziliensis
author Gomes, Clayson Moura
author_facet Gomes, Clayson Moura
author_role author
dc.contributor.advisor1.fl_str_mv Oliveira, Milton Adriano Pelli de
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/2152513705182408
dc.contributor.referee1.fl_str_mv Cruvinel, Wilson de Melo
dc.contributor.referee2.fl_str_mv Pfrimer, Irmtraut Araci Hoffmann
dc.contributor.referee3.fl_str_mv Oliveira, Milton Adriano Pelli de
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/8550177354539916
dc.contributor.author.fl_str_mv Gomes, Clayson Moura
contributor_str_mv Oliveira, Milton Adriano Pelli de
Cruvinel, Wilson de Melo
Pfrimer, Irmtraut Araci Hoffmann
Oliveira, Milton Adriano Pelli de
dc.subject.por.fl_str_mv Leishmania (Viannia) braziliensis
Leishmaniose cutânea
Leishmaniose mucosa
Células mononucleares
Citocina
topic Leishmania (Viannia) braziliensis
Leishmaniose cutânea
Leishmaniose mucosa
Células mononucleares
Citocina
Human
Leishmaniasis
CIENCIAS BIOLOGICAS::IMUNOLOGIA
dc.subject.eng.fl_str_mv Human
Leishmaniasis
dc.subject.cnpq.fl_str_mv CIENCIAS BIOLOGICAS::IMUNOLOGIA
description Introduction: Leishmaniasis is a tropical zoonoses that is endemic, causing different clinical forms including cutaneous, diffuse, disseminated, mucosal and visceral manifestations. The L. (V.) braziliensis is the most common parasite found in cutaneous leishmaniasis in Brazil and is the major agent for the mucosal leishmaniasis. The manifestation of the disease and the clinical forms are dependent on several factors related between the parasite and host. Objective: The aim of this study was to compare the ability of amastigote parasite isolated from patients with cutaneous or mucosal leishmaniasis to stimulate the production of cytokines in peripheral blood mononuclear cells cultures (PBMC) obtained from health donors. Methods: Isolates of patients with cutaneous or mucosal lesion were inoculated in IFNγ knockout mice to obtain amastigotes, which were purifyed by density using Percoll. The PBMCs from healthy individuals were separated by density using Ficoll. The cells were incubated in cultures at different times with amastigotes and then the supernatant were collect to quantify cytokines by ELISA or cells that are used to quantify cytokines using the real time PCR. Results: PBMCs produced higher amounts of IL-1β, IL-6, IL-10 and TGFβ in cultures after stimulation with amastigotes than uninfected controls. When comparing isolates from cutaneous or mucosal disease it was not found differerence regarding to the production of IL-6, IL-10 and TGFβ, but amastigotes from patients with cutaneous leishmaniasis induced more IL-1β than in parasites obtained from mucosal lesion. Production of IFNγ IL17, and TNF was was not detected at different times after stimulation with L. (V.) braziliensis amastigotes. Conclusion: The results suggest that amastigotes of patients with cutaneous leishmaniasis interact with innate immunity cells by inducing the production of proinflammatory or anti-inflammatory and isolated from mucosal lesions induce less IL-1 than parasites obtained from skin lesions. The greatest amount of IL-1 promotes an inflammatory response with migration of cells to the site of infection, so a low xvii production would cause a slower disease and would prejudice an effective acquired response. Thus, the parasite would be able to survive longer in host in a silent way.
publishDate 2012
dc.date.issued.fl_str_mv 2012-02-03
dc.date.accessioned.fl_str_mv 2014-09-26T21:28:37Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
status_str publishedVersion
dc.identifier.citation.fl_str_mv GOMES, Clayson Moura. Produção de citocinas por células mononucleares humanas estimuladas por formas amastigotas de Leishmania(Viannia) braziliensis. 2012. 117 f. Dissertação (Mestrado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2012.
dc.identifier.uri.fl_str_mv http://repositorio.bc.ufg.br/tede/handle/tede/3199
dc.identifier.dark.fl_str_mv ark:/38995/0013000001p61
identifier_str_mv GOMES, Clayson Moura. Produção de citocinas por células mononucleares humanas estimuladas por formas amastigotas de Leishmania(Viannia) braziliensis. 2012. 117 f. Dissertação (Mestrado em Medicina Tropical e Saúde Publica) - Universidade Federal de Goiás, Goiânia, 2012.
ark:/38995/0013000001p61
url http://repositorio.bc.ufg.br/tede/handle/tede/3199
dc.language.iso.fl_str_mv por
language por
dc.relation.program.fl_str_mv 6085308344741430434
dc.relation.confidence.fl_str_mv 600
600
600
600
600
dc.relation.department.fl_str_mv -7769011444564556288
dc.relation.cnpq.fl_str_mv 5989919188376747614
dc.relation.sponsorship.fl_str_mv 2075167498588264571
-2555911436985713659
dc.relation.references.por.fl_str_mv Ahmed S, Colmenares M, Soong L, Goldsmith-Pestana K, Munstermann L, Molina R, McMahon-Pratt D 2003. Intradermal infection model for pathogenesis and vaccine studies of murine visceral leishmaniasis. Infect Immun, 71, 401-410. Alborzi A, Pouladfar GR, Fakhar M, Motazedian MH, Hatam GR, Kadivar MR 2008. Isolation of Leishmania tropica from a patient with visceral leishmaniasis and disseminated cutaneous leishmaniasis, southern Iran. Am J Trop Med Hyg, 79, 435-437. Alcolea PJ, Alonso A, Gomez MJ, Moreno I, Dominguez M, Parro V, Larraga V 2010. Transcriptomics throughout the life cycle of Leishmania infantum: high down-regulation rate in the amastigote stage. Int J Parasitol, 40, 1497-1516. Amato VS, Tuon FF, Siqueira AM, Nicodemo AC, Neto VA 2007. Treatment of mucosal leishmaniasis in Latin America: systematic review. Am J Trop Med Hyg, 77, 266-274. Anderson CF, Stumhofer JS, Hunter CA, Sacks D 2009. IL-27 regulates IL-10 and IL-17 from CD4+ cells in nonhealing Leishmania major infection. J Immunol, 183, 4619-4627. Assier E, Boissier MC, Dayer JM 2010. Interleukin-6: from identification of the cytokine to development of targeted treatments. Joint Bone Spine, 77, 532-536. Avila JL, Rojas M, Rieber M 1984. Antibodies to laminin in American cutaneous leishmaniasis. Infect Immun, 43, 402-406. Ávila LR, Gomes CM, Tomé FD, Vinaud MC, Pereira LIA, Duarte FB, Ribeiro-Dias F, Dorta ML, Uliana SR, Oliveira MAP 2012. Leishmania (Viannia) braziliensis isolated 45 from mucosal lesion express more thiol-specific antioxidant protein than parasites isolated from cutaneous lesion. Manuscrito em preparação. Bacellar O, Faria D, Nascimento M, Cardoso TM, Gollob KJ, Dutra WO, Scott P, Carvalho EM 2009. Interleukin 17 production among patients with American cutaneous leishmaniasis. Journal of Infectious Disesases, 200, n. 1, 75-78. Bacellar O, Lessa H, Schriefer A, Machado P, Ribeiro de Jesus A, Dutra WO, Gollob KJ, Carvalho EM 2002. Up-regulation of Th1-type responses in mucosal leishmaniasis patients. Infect Immun, 70, 6734-6740. Bajenoff M, Breart B, Huang AY, Qi H, Cazareth J, Braud VM, Germain RN, Glaichenhaus N 2006. Natural killer cell behavior in lymph nodes revealed by static and real-time imaging. J Exp Med, 203, 619-631. Banuls AL, Hide M, Prugnolle F 2007. Leishmania and the leishmaniases: a parasite genetic update and advances in taxonomy, epidemiology and pathogenicity in humans. Adv Parasitol, 64, 1-109. Barlow JL, McKenzie AN 2011. Nuocytes: expanding the innate cell repertoire in type-2 immunity. J Leukoc Biol. Barral A, Jesus AR, Almeida RP, Carvalho EM, Barral-Netto M, Costa JM, Badaro R, Rocha H, Johnson WD 1987. Evaluation of T-cell subsets in the lesion infiltrates of human cutaneous and mucocutaneous leishmaniasis. Parasite Immunol, 9, 487-497. Bauernfeind F, Ablasser A, Bartok E, Kim S, Schmid-Burgk J, Cavlar T, Hornung V 2011a. Inflammasomes: current understanding and open questions. Cell Mol Life Sci, 68, 765-783. 46 Bauernfeind F, Bartok E, Rieger A, Franchi L, Nunez G, Hornung V 2011b. Cutting edge: reactive oxygen species inhibitors block priming, but not activation, of the NLRP3 inflammasome. J Immunol, 187, 613-617. Beil WJ, Meinardus-Hager G, Neugebauer DC, Sorg C 1992. Differences in the onset of the inflammatory response to cutaneous leishmaniasis in resistant and susceptible mice. J Leukoc Biol, 52, 135-142. Belkaid Y, Piccirillo CA, Mendez S, Shevach EM, Sacks DL 2002. CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity. Nature, 420, 502-507. Boaventura VS, Santos CS, Cardoso CR, de Andrade J, Dos Santos WL, Clarencio J, Silva JS, Borges VM, Barral-Netto M, Brodskyn CI, Barral A 2010. Human mucosal leishmaniasis: neutrophils infiltrate areas of tissue damage that express high levels of Th17-related cytokines. Eur J Immunol, 40, 2830-2836. Bogdan C, Rollinghoff M, Diefenbach A 2000. The role of nitric oxide in innate immunity. Immunol Rev, 173, 17-26. Brasil M 2007. Manual de Vigilância da Leishmaniose Tegumentar Americana. 2nd Ed. ed., 2nd Ed. ed., Ministério da Saúde, Brasilia, 182 pp. Brasil MdSd 2006. Atlas de Leishmaniose tegumentar Americana - diagnósticos clínico e diferencial. Ministério da Saúde, Brasilia, 138 pp. Buxbaum LU, Scott P 2005. Interleukin 10- and Fcgamma receptor-deficient mice resolve Leishmania mexicana lesions. Infect Immun, 73, 2101-2108. 47 Buxbaum LU, Uzonna JE, Goldschmidt MH, Scott P 2002. Control of New World cutaneous leishmaniasis is IL-12 independent but STAT4 dependent. Eur J Immunol, 32, 3206-3215. Cabrera M, Shaw MA, Sharples C, Williams H, Castes M, Convit J, Blackwell JM 1995. Polymorphism in tumor necrosis factor genes associated with mucocutaneous leishmaniasis. J Exp Med, 182, 1259-1264. Caceres-Dittmar G, Tapia FJ, Sanchez MA, Yamamura M, Uyemura K, Modlin RL, Bloom BR, Convit J 1993. Determination of the cytokine profile in American cutaneous leishmaniasis using the polymerase chain reaction. Clin Exp Immunol, 91, 500-505. Campanelli AP, Roselino AM, Cavassani KA, Pereira MS, Mortara RA, Brodskyn CI, Goncalves HS, Belkaid Y, Barral-Netto M, Barral A, Silva JS 2006. CD4+CD25+ T cells in skin lesions of patients with cutaneous leishmaniasis exhibit phenotypic and functional characteristics of natural regulatory T cells. J Infect Dis, 193, 1313-1322. Carvalho EM, Barral A, Costa JM, Bittencourt A, Marsden P 1994. Clinical and immunopathological aspects of disseminated cutaneous leishmaniasis. Acta Trop, 56, 315-325. Carvalho EM, Correia Filho D, Bacellar O, Almeida RP, Lessa H, Rocha H 1995. Characterization of the immune response in subjects with self-healing cutaneous leishmaniasis. Am J Trop Med Hyg, 53, 273-277. Cassatella MA 1995. The production of cytokines by polymorphonuclear neutrophils. Immunol Today, 16, 21-26. Castellucci L, Menezes E, Oliveira J, Magalhaes A, Guimaraes LH, Lessa M, Ribeiro S, Reale J, Noronha EF, Wilson ME, Duggal P, Beaty TH, Jeronimo S, Jamieson SE, Bales A, Blackwell JM, de Jesus AR, Carvalho EM 2006. IL6 -174 G/C promoter 48 polymorphism influences susceptibility to mucosal but not localized cutaneous leishmaniasis in Brazil. J Infect Dis, 194, 519-527. Chen M, Wang H, Chen W, Meng G 2011. Regulation of adaptive immunity by the NLRP3 inflammasome. Int Immunopharmacol, 11, 549-554. Clem A 2010. A current perspective on leishmaniasis. J Glob Infect Dis, 2, 124-126. Colotti G, Ilari A 2010. Polyamine metabolism in Leishmania: from arginine to trypanothione. Amino Acids, 40, 269-285. Convit JU, M. 1993. Antigen-specific immunodeficiency and its relation to the spectrum of American cutaneous leishmaniasis. Biol Res, 26, 159-166. Costa DL, Carregaro V, Lima-Junior DS, Silva NM, Milanezi CM, Cardoso CR, Giudice A, de Jesus AR, Carvalho EM, Almeida RP, Silva JS 2011. BALB/c mice infected with antimony treatment refractory isolate of Leishmania braziliensis present severe lesions due to IL-4 production. PLoS Negl Trop Dis, 5, e965. Costa JM, Vale KC, Cecilio IN, Osaki NK, Netto EM, Tada MS, Franca F, Barreto MC, Marsden PD 1987. Psychosocial and stigmatizing aspects of mucocutaneous leishmaniasis. Rev Soc Bras Med Trop, 20, 77-81. Cruvinel WM, Mesquita D, Jr., Araujo JA, Catelan TT, de Souza AW, da Silva NP, Andrade LE 2010. Immune system - part I. Fundamentals of innate immunity with emphasis on molecular and cellular mechanisms of inflammatory response. Rev Bras Reumatol, 50, 434-461. 49 Cuervo P, Cupolillo E, Nehme N, Hernandez V, Saravia N, Fernandes O 2004. Leishmania (Viannia): genetic analysis of cutaneous and mucosal strains isolated from the same patient. Exp Parasitol, 108, 59-66. Cupolillo E, Brahim LR, Toaldo CB, de Oliveira-Neto MP, de Brito ME, Falqueto A, de Farias Naiff M, Grimaldi G, Jr. 2003. Genetic polymorphism and molecular epidemiology of Leishmania (Viannia) braziliensis from different hosts and geographic areas in Brazil. J Clin Microbiol, 41, 3126-3132. Daneshbod Y, Oryan A, Davarmanesh M, Shirian S, Negahban S, Aledavood A, Davarpanah MA, Soleimanpoor H, Daneshbod K 2011. Clinical, histopathologic, and cytologic diagnosis of mucosal leishmaniasis and literature review. Arch Pathol Lab Med, 135, 478-482. Das J, Ren G, Zhang L, Roberts AI, Zhao X, Bothwell AL, Van Kaer L, Shi Y, Das G 2009. Transforming growth factor beta is dispensable for the molecular orchestration of Th17 cell differentiation. J Exp Med, 206, 2407-2416. David CV, Craft N 2009. Cutaneous and mucocutaneous leishmaniasis. Dermatol Ther, 22, 491-502. de Baey A, Mende I, Riethmueller G, Baeuerle PA 2001. Phenotype and function of human dendritic cells derived from M-DC8(+) monocytes. Eur J Immunol, 31, 1646-1655. de Magalhaes AV, Moraes MA, Raick AN, Llanos-Cuentas A, Costa JM, Cuba CC, Marsden PD 1986. Histopathology of cutaneous leishmaniasis caused by Leishmania braziliensis braziliensis . 4.Histopathological classification. Rev Inst Med Trop Sao Paulo, 28, 421-430. 50 de Moura TR, Novais FO, Oliveira F, Clarencio J, Noronha A, Barral A, Brodskyn C, de Oliveira CI 2005. Toward a novel experimental model of infection to study American cutaneous leishmaniasis caused by Leishmania braziliensis. Infect Immun, 73, 5827-5834. de Souza-Neto SM, Carneiro CM, Vieira LQ, Afonso LC 2004. Leishmania braziliensis: partial control of experimental infection by interleukin-12 p40 deficient mice. Mem Inst Oswaldo Cruz, 99, 289-294. de Souza Carmo EV, Katz S, Barbieri CL 2010. Neutrophils reduce the parasite burden in Leishmania (Leishmania) amazonensis-infected macrophages. PLoS One, 5, e13815. DeKrey GK, Lima HC, Titus RG 1998. Analysis of the immune responses of mice to infection with Leishmania braziliensis. Infect Immun, 66, 827-829. Derouin F 2007. Parasitic infection in immunocompromised patients. Rev Prat, 57, 167-173. Diaz NL, Arvelaez FA, Zerpa O, Tapia FJ 2006. Inducible nitric oxide synthase and cytokine pattern in lesions of patients with American cutaneous leishmaniasis. Clin Exp Dermatol, 31, 114-117. Dinarello CA 2011. Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood, 117, 3720-3732. Dominguez M, Moreno I, Aizpurua C, Torano A 2003. Early mechanisms of Leishmania infection in human blood. Microbes Infect, 5, 507-513. 51 Doyle MA, MacRae JI, De Souza DP, Saunders EC, McConville MJ, Likic VA 2009. LeishCyc: a biochemical pathways database for Leishmania major. BMC Syst Biol, 3, 57. Espinosa V, Rivera A 2011. Cytokines and the regulation of fungus-specific CD4 T cell differentiation. Cytokine. Esterre P, Dedet JP, Frenay C, Chevallier M, Grimaud JA 1992. Cell populations in the lesion of human cutaneous leishmaniasis: a light microscopical, immunohistochemical and ultrastructural study. Virchows Arch A Pathol Anat Histopathol, 421, 239-247. Faria DR, Gollob KJ, Barbosa J, Jr., Schriefer A, Machado PR, Lessa H, Carvalho LP, Romano-Silva MA, de Jesus AR, Carvalho EM, Dutra WO 2005. Decreased in situ expression of interleukin-10 receptor is correlated with the exacerbated inflammatory and cytotoxic responses observed in mucosal leishmaniasis. Infect Immun, 73, 7853-7859. Filardy AA, Pires DR, DosReis GA 2011. Macrophages and neutrophils cooperate in immune responses to Leishmania infection. Cell Mol Life Sci, 68, 1863-1870. Ghaemi-Oskouie F, Shi Y 2011. The role of uric acid as an endogenous danger signal in immunity and inflammation. Curr Rheumatol Rep, 13, 160-166. Ghoreschi K, Laurence A, Yang XP, Tato CM, McGeachy MJ, Konkel JE, Ramos HL, Wei L, Davidson TS, Bouladoux N, Grainger JR, Chen Q, Kanno Y, Watford WT, Sun HW, Eberl G, Shevach EM, Belkaid Y, Cua DJ, Chen W, O'Shea JJ 2010. Generation of pathogenic T(H)17 cells in the absence of TGF-beta signalling. Nature, 467, 967-971. Giudice A, Camada I, Leopoldo PT, Pereira JM, Riley LW, Wilson ME, Ho JL, de Jesus AR, Carvalho EM, Almeida RP 2007. Resistance of Leishmania (Leishmania) 52 amazonensis and Leishmania (Viannia) braziliensis to nitric oxide correlates with disease severity in Tegumentary Leishmaniasis. BMC Infect Dis, 7, 7. Gomes-Silva A, de Cassia Bittar R, Dos Santos Nogueira R, Amato VS, da Silva Mattos M, Oliveira-Neto MP, Coutinho SG, Da-Cruz AM 2007. Can interferon-gamma and interleukin-10 balance be associated with severity of human Leishmania (Viannia) braziliensis infection? Clin Exp Immunol, 149, 440-444. Gordon S 2003. Alternative activation of macrophages. Nat Rev Immunol, 3, 23-35. Goto H, Lindoso JA 2010. Current diagnosis and treatment of cutaneous and mucocutaneous leishmaniasis. Expert Rev Anti Infect Ther, 8, 419-433. Grevelink SA, Lerner EA 1996. Leishmaniasis. J Am Acad Dermatol, 34, 257-272. Guerra JA, Prestes SR, Silveira H, Coelho LI, Gama P, Moura A, Amato V, Barbosa MG, Ferreira LC 2011. Mucosal Leishmaniasis caused by Leishmania (Viannia) braziliensis and Leishmania (Viannia) guyanensis in the Brazilian Amazon. PLoS Negl Trop Dis, 5, e980. Guimaraes-Costa AB, Nascimento MT, Froment GS, Soares RP, Morgado FN, Conceicao-Silva F, Saraiva EM 2009. Leishmania amazonensis promastigotes induce and are killed by neutrophil extracellular traps. Proc Natl Acad Sci U S A, 106, 6748-6753. Gutierrez Y, Salinas GH, Palma G, Valderrama LB, Santrich CV, Saravia NG 1991. Correlation between histopathology, immune response, clinical presentation, and evolution in Leishmania braziliensis infection. Am J Trop Med Hyg, 45, 281-289. 53 Hawrylowicz CM 2005. Regulatory T cells and IL-10 in allergic inflammation. J Exp Med, 202, 1459-1463. Heinzel FP, Sadick MD, Holaday BJ, Coffman RL, Locksley RM 1989. Reciprocal expression of interferon gamma or interleukin 4 during the resolution or progression of murine leishmaniasis. Evidence for expansion of distinct helper T cell subsets. J Exp Med, 169, 59-72. Hernandez-Ruiz J, Salaiza-Suazo N, Carrada G, Escoto S, Ruiz-Remigio A, Rosenstein Y, Zentella A, Becker I 2010. CD8 cells of patients with diffuse cutaneous leishmaniasis display functional exhaustion: the latter is reversed, in vitro, by TLR2 agonists. PLoS Negl Trop Dis, 4, e871. Herwaldt BL 1999. Leishmaniasis. Lancet, 354, 1191-1199. Hofmann SR, Ettinger R, Zhou YJ, Gadina M, Lipsky P, Siegel R, Candotti F, O'Shea JJ 2002. Cytokines and their role in lymphoid development, differentiation and homeostasis. Curr Opin Allergy Clin Immunol, 2, 495-506. Jones TC, Johnson WD, Jr., Barretto AC, Lago E, Badaro R, Cerf B, Reed SG, Netto EM, Tada MS, Franca TF, et al. 1987. Epidemiology of American cutaneous leishmaniasis due to Leishmania braziliensis braziliensis. J Infect Dis, 156, 73-83. Kautz-Neu K, Kostka SL, Dinges S, Iwakura Y, Udey MC, von Stebut E 2010. IL-1 signalling is dispensable for protective immunity in Leishmania-resistant mice. Exp Dermatol, 20, 76-78. Kimblin N, Peters N, Debrabant A, Secundino N, Egen J, Lawyer P, Fay MP, Kamhawi S, Sacks D 2008. Quantification of the infectious dose of Leishmania major transmitted to the skin by single sand flies. Proc Natl Acad Sci U S A, 105, 10125-10130. 54 Kimura A, Kishimoto T 2011. Th17 cells in inflammation. Int Immunopharmacol, 11, 319-322. Kostka SL, Knop J, Konur A, Udey MC, von Stebut E 2006. Distinct roles for IL-1 receptor type I signaling in early versus established Leishmania major infections. J Invest Dermatol, 126, 1582-1589. Kropf P, Fuentes JM, Fahnrich E, Arpa L, Herath S, Weber V, Soler G, Celada A, Modolell M, Muller I 2005. Arginase and polyamine synthesis are key factors in the regulation of experimental leishmaniasis in vivo. FASEB J, 19, 1000-1002. Kryczek I, Wei S, Vatan L, Escara-Wilke J, Szeliga W, Keller ET, Zou W 2007. Cutting edge: opposite effects of IL-1 and IL-2 on the regulation of IL-17+ T cell pool IL-1 subverts IL-2-mediated suppression. J Immunol, 179, 1423-1426. Lachmann HJ, Quartier P, So A, Hawkins PN 2011. The emerging role of interleukin-1beta in autoinflammatory diseases. Arthritis Rheum, 63, 314-324. Lane T, Lachmann HJ 2011. The Emerging Role of Interleukin-1beta in Autoinflammatory Diseases. Curr Allergy Asthma Rep. Lang T, Goyard S, Lebastard M, Milon G 2005. Bioluminescent Leishmania expressing luciferase for rapid and high throughput screening of drugs acting on amastigote-harbouring macrophages and for quantitative real-time monitoring of parasitism features in living mice. Cell Microbiol, 7, 383-392. Lei SM, Romine NM, Beetham JK 2010. Population changes in Leishmania chagasi promastigote developmental stages due to serial passage. J Parasitol, 96, 1134-1138. 55 Leite PM, Gomes RS, Figueiredo AB, Fietto JLR, Melo MN, Ribeiro-Dias F, Oliveira MAP, Rabello A, Afonso LCC 2012. Ecto-nucleotidasic activity, infectivity and clinical outcome in Leishmania braziliensis isolates. Artigo submetido para publicação. Liddiard K, Rosas M, Davies LC, Jones SA, Taylor PR 2011. Macrophage heterogeneity and acute inflammation. Eur J Immunol, 41, 2503-2508. Liese J, Schleicher U, Bogdan C 2008. The innate immune response against Leishmania parasites. Immunobiology, 213, 377-387. Liew FY, O'Donnell CA 1993. Immunology of leishmaniasis. Adv Parasitol, 32, 161-259. Maioli TU, Takane E, Arantes RM, Fietto JL, Afonso LC 2004. Immune response induced by New World Leishmania species in C57BL/6 mice. Parasitol Res, 94, 207-212. Maizels RM, Pearce EJ, Artis D, Yazdanbakhsh M, Wynn TA 2009. Regulation of pathogenesis and immunity in helminth infections. J Exp Med, 206, 2059-2066. Maretti-Mira AC, de Pinho Rodrigues KM, de Oliveira-Neto MP, Pirmez C, Craft N 2011. MMP-9 activity is induced by Leishmania braziliensis infection and correlates with mucosal leishmaniasis. Acta Trop. Marsden PD 1994. Mucosal leishmaniasis due to Leishmania (Viannia) braziliensis L(V)b in Três Braços, Bahia-Brazil. Rev Soc Bras Med Trop, 27, 93-101. Martinez-Arends A, Tapia FJ, Caceres-Dittmar G, Mosca W, Valecillos L, Convit J 1991. Immunocytochemical characterization of immune cells in lesions of American cutaneous leishmaniasis using novel T cell markers. Acta Trop, 49, 271-280. 56 McMahon-Pratt D, Alexander J 2004. Does the Leishmania major paradigm of pathogenesis and protection hold for New World cutaneous leishmaniases or the visceral disease? Immunol Rev, 201, 206-224. Meddeb-Garnaoui A, Zrelli H, Dellagi K 2009. Effects of tropism and virulence of Leishmania parasites on cytokine production by infected human monocytes. Clin Exp Immunol, 155, 199-206. Mendez S, Reckling SK, Piccirillo CA, Sacks D, Belkaid Y 2004. Role for CD4(+) CD25(+) regulatory T cells in reactivation of persistent leishmaniasis and control of concomitant immunity. J Exp Med, 200, 201-210. Mitropoulos P, Konidas P, Durkin-Konidas M 2011. New World cutaneous leishmaniasis: updated review of current and future diagnosis and treatment. J Am Acad Dermatol, 63, 309-322. Modolell M, Choi BS, Ryan RO, Hancock M, Titus RG, Abebe T, Hailu A, Muller I, Rogers ME, Bangham CR, Munder M, Kropf P 2009. Local suppression of T cell responses by arginase-induced L-arginine depletion in nonhealing leishmaniasis. PLoS Negl Trop Dis, 3, e480. Mougneau E, Bihl F, Glaichenhaus N 2011. Cell biology and immunology of Leishmania. Immunol Rev, 240, 286-296. Mucida D, Cheroutre H 2007. TGFbeta and retinoic acid intersect in immune-regulation. Cell Adh Migr, 1, 142-144. Mukbel RM, Patten C, Jr., Gibson K, Ghosh M, Petersen C, Jones DE 2007. Macrophage killing of Leishmania amazonensis amastigotes requires both nitric oxide and superoxide. Am J Trop Med Hyg, 76, 669-675. 57 Murray HW 2008. Accelerated control of visceral Leishmania donovani infection in interleukin-6-deficient mice. Infect Immun, 76, 4088-4091. Novoa R, Bacellar O, Nascimento M, Cardoso TM, Ramasawmy R, Oliveira WN, Schriefer A, Carvalho EM 2010. IL-17 and Regulatory Cytokines (IL-10 and IL-27) in L. braziliensis Infection. Parasite Immunol, 33, 132-136. Nylen S, Gautam S 2010. Immunological perspectives of leishmaniasis. J Glob Infect Dis, 2, 135-146. Oliveira F, Bafica A, Rosato AB, Favali CB, Costa JM, Cafe V, Barral-Netto M, Barral A 2011. Lesion Size Correlates with Leishmania Antigen-Stimulated TNF-Levels in Human Cutaneous Leishmaniasis. Am J Trop Med Hyg, 85, 70-73. Oliveira MA, Pires Ada S, de Bastos RP, Lima GM, Pinto SA, Pereira LI, Pereira AJ, Abrahamsohn Ide A, Dorta ML, Ribeiro-Dias F 2010. Leishmania spp. parasite isolation through inoculation of patient biopsy macerates in interferon gamma knockout mice. Rev Inst Med Trop Sao Paulo, 52, 83-88. Pappu BP, Angkasekwinai P, Dong C 2008. Regulatory mechanisms of helper T cell differentiation: new lessons learned from interleukin 17 family cytokines. Pharmacol Ther, 117, 374-384. Passos STS, J. S.; O'hara, A. C.; Sehy, D.; Stumhofer, J. S.; Hunter, C. A. 2010. IL-6 promotes NK cell production of IL-17 during toxoplasmosis. Journal of Immunology, 184, 1776-1783. Passos VM, Lasmar EB, Gontijo CM, Fernandes O, Degrave W 1996. Natural infection of a domestic cat (Felis domesticus) with Leishmania (Viannia) in the metropolitan region of Belo Horizonte, State of Minas Gerais, Brazil. Mem Inst Oswaldo Cruz, 91, 19-20. 58 Pereira CG, Silva AL, de Castilhos P, Mastrantonio EC, Souza RA, Romao RP, Rezende RJ, Pena JD, Beletti ME, Souza MA 2009a. Different isolates from Leishmania braziliensis complex induce distinct histopathological features in a murine model of infection. Vet Parasitol, 165, 231-240. Pereira LI, Dorta ML, Pereira AJ, Bastos RP, Oliveira MA, Pinto SA, Galdino H, Jr., Mayrink W, Barcelos W, Toledo VP, Lima GM, Ribeiro-Dias F 2009b. Increase of NK cells and proinflammatory monocytes are associated with the clinical improvement of diffuse cutaneous leishmaniasis after immunochemotherapy with BCG/Leishmania antigens. Am J Trop Med Hyg, 81, 378-383. Peters N, Sacks D 2006. Immune privilege in sites of chronic infection: Leishmania and regulatory T cells. Immunol Rev, 213, 159-179. Phelan SA 1999. AOP2 (antioxidant protein 2): structure and function of a unique thiol-specific antioxidant. Antioxid Redox Signal, 1, 571-584. Pirmez C, Cooper C, Paes-Oliveira M, Schubach A, Torigian VK, Modlin RL 1990. Immunologic responsiveness in American cutaneous leishmaniasis lesions. J Immunol, 145, 3100-3104. Pirmez C, Yamamura M, Uyemura K, Paes-Oliveira M, Conceicao-Silva F, Modlin RL 1993. Cytokine patterns in the pathogenesis of human leishmaniasis. J Clin Invest, 91, 1390-1395. Pitta MG, Romano A, Cabantous S, Henri S, Hammad A, Kouriba B, Argiro L, el Kheir M, Bucheton B, Mary C, El-Safi SH, Dessein A 2009. IL-17 and IL-22 are associated with protection against human kala azar caused by Leishmania donovani. J Clin Invest, 119, 2379-2387. 59 Pluddemann A, Mukhopadhyay S, Gordon S 2011. Innate immunity to intracellular pathogens: macrophage receptors and responses to microbial entry. Immunol Rev, 240, 11-24. Reynolds JM, Angkasekwinai P, Dong C 2010. IL-17 family member cytokines: regulation and function in innate immunity. Cytokine Growth Factor Rev, 21, 413-423. Rocha FJ, Schleicher U, Mattner J, Alber G, Bogdan C 2007. Cytokines, signaling pathways, and effector molecules required for the control of Leishmania (Viannia) braziliensis in mice. Infect Immun, 75, 3823-3832. Roshick C, Wood H, Caldwell HD, McClarty G 2006. Comparison of gamma interferon-mediated antichlamydial defense mechanisms in human and mouse cells. Infect Immun, 74, 225-238. Sabat R, Grutz G, Warszawska K, Kirsch S, Witte E, Wolk K, Geginat J 2010. Biology of interleukin-10. Cytokine Growth Factor Rev, 21, 331-344. Sacks D, Anderson C 2004. Re-examination of the immunosuppressive mechanisms mediating non-cure of Leishmania infection in mice. Immunol Rev, 201, 225-238. Salay G, Dorta ML, Santos NM, Mortara RA, Brodskyn C, Oliveira CI, Barbieri CL, Rodrigues MM 2007. Testing of four Leishmania vaccine candidates in a mouse model of infection with Leishmania (Viannia) braziliensis, the main causative agent of cutaneous leishmaniasis in the New World. Clin Vaccine Immunol, 14, 1173-1181. Salhi A, Rodrigues V, Jr., Santoro F, Dessein H, Romano A, Castellano LR, Sertorio M, Rafati S, Chevillard C, Prata A, Alcais A, Argiro L, Dessein A 2008. Immunological and genetic evidence for a crucial role of IL-10 in cutaneous lesions in humans infected with Leishmania braziliensis. J Immunol, 180, 6139-6148. 60 Sanchez JL, Diniega BM, Small JW, Miller RN, Andujar JM, Weina PJ, Lawyer PG, Ballou WR, Lovelace JK 1992. Epidemiologic investigation of an outbreak of cutaneous leishmaniasis in a defined geographic focus of transmission. Am J Trop Med Hyg, 47, 47-54. Santarlasci V, Maggi L, Capone M, Frosali F, Querci V, De Palma R, Liotta F, Cosmi L, Maggi E, Romagnani S, Annunziato F 2009. TGF-beta indirectly favors the development of human Th17 cells by inhibiting Th1 cells. Eur J Immunol, 39, 207-215. Saravia NG, Weigle K, Segura I, Giannini SH, Pacheco R, Labrada LA, Goncalves A 1990. Recurrent lesions in human Leishmania braziliensis infection--reactivation or reinfection? Lancet, 336, 398-402. Sartori A, Oliveira MA, Scott P, Trinchieri G 1997. Metacyclogenesis modulates the ability of Leishmania promastigotes to induce IL-12 production in human mononuclear cells. J Immunol, 159, 2849-2857. Scharton-Kersten T, Nakajima H, Yap G, Sher A, Leonard WJ 1998. Infection of mice lacking the common cytokine receptor gamma-chain (gamma(c)) reveals an unexpected role for CD4+ T lymphocytes in early IFN-gamma-dependent resistance to Toxoplasma gondii. J Immunol, 160, 2565-2569. Scharton TM, Scott P 1993. Natural killer cells are a source of interferon gamma that drives differentiation of CD4+ T cell subsets and induces early resistance to Leishmania major in mice. J Exp Med, 178, 567-577. Scott PA, D.; Uzonna, J.; Zaph, C. 2004. The development of effector and memory T cells in cutaneous leishmaniasis: the implications for vaccine development. Immunological Reviews, 201, 318-338. 61 Sethuraman GV, K. Sharma 2008. Indian mucosal leishmaniasis due to Leishmania donovani infection. N Engl J Med, 358, 313-315. Shakya N, Sane SA, Vishwakarma P, Bajpai P, Gupta S 2011. Improved treatment of visceral leishmaniasis (kala-azar) by using combination of ketoconazole, miltefosine with an immunomodulator-Picroliv. Acta Trop. Silveira FT, Lainson R, Corbett CE 2004. Clinical and immunopathological spectrum of American cutaneous leishmaniasis with special reference to the disease in Amazonian Brazil: a review. Mem Inst Oswaldo Cruz, 99, 239-251. Silveira FT, Laison R, Corbett CE 2005. Further observations on clinical, histopathological, and immunological features of borderline disseminated cutaneous leishmaniasis caused by Leishmania (Leishmania) amazonensis. Mem Inst Oswaldo Cruz, 100, 525-534. Silveira FT, Lainson R, De Castro Gomes CM, Laurenti MD, Corbett CE 2009. Immunopathogenic competences of Leishmania (V.) braziliensis and L. (L.) amazonensis in American cutaneous leishmaniasis. Parasite Immunol, 31, 423-431. Singh S, Sharma U, Mishra J 2011. Post-kala-azar dermal leishmaniasis: recent developments. Int J Dermatol, 50, 1099-1108. Skeiky YA, Guderian JA, Benson DR, Bacelar O, Carvalho EM, Kubin M, Badaro R, Trinchieri G, Reed SG 1995. A recombinant Leishmania antigen that stimulates human peripheral blood mononuclear cells to express a Th1-type cytokine profile and to produce interleukin 12. J Exp Med, 181, 1527-1537. Souza AS, Giudice A, Pereira JM, Guimaraes LH, de Jesus AR, de Moura TR, Wilson ME, Carvalho EM, Almeida RP 2010. Resistance of Leishmania (Viannia) braziliensis 62 to nitric oxide: correlation with antimony therapy and TNF-alpha production. BMC Infect Dis, 10, 209. Strutt TM, McKinstry KK, Swain SL 2011. Control of innate immunity by memory CD4 T cells. Adv Exp Med Biol, 780, 57-68. Tabatabaie FGf, FF. Dalimi,A. Sharifi, Z. Zavaran Hoseini, A. 2007. Cloning and Sequencing of Leishmania major Thiol-Specific-Antioxidant Antigen (TSA) Gene. Iranian Journal of Parasitology, 2, nº 4. Tandon A, Tovey JC, Sharma A, Gupta R, Mohan RR 2010. Role of transforming growth factor Beta in corneal function, biology and pathology. Curr Mol Med, 10, 565-578. Tansey MG, Szymkowski DE 2009. The TNF superfamily in 2009: new pathways, new indications, and new drugs. Drug Discov Today, 14, 1082-1088. Tapia FJ, Caceres-Dittmar G, Sanchez MA 1994. Inadequate epidermal homing leads to tissue damage in human cutaneous leishmaniasis. Immunol Today, 15, 160-165. Trinchieri G 2003. Interleukin-12 and the regulation of innate resistance and adaptive immunity. Nat Rev Immunol, 3, 133-146. Underhill DM, Ozinsky A 2002. Phagocytosis of microbes: complexity in action. Annu Rev Immunol, 20, 825-852. Van Assche T, Deschacht M, da Luz RA, Maes L, Cos P 2011. Leishmania-macrophage interactions: Insights into the redox biology. Free Radic Biol Med, 51, 337-351. 63 Veldhoen M, Hocking RJ, Atkins CJ, Locksley RM, Stockinger B 2006. TGFbeta in the context of an inflammatory cytokine milieu supports de novo differentiation of IL-17-producing T cells. Immunity, 24, 179-189. Vendrame CM, Souza LD, Carvalho MD, Salgado K, Carvalho EM, Goto H 2010. Insulin-like growth factor-I induced and constitutive arginase activity differs among isolates of Leishmania derived from patients with diverse clinical forms of Leishmania braziliensis infection. Trans R Soc Trop Med Hyg, 104, 566-568. Volpini AC, Passos VM, Oliveira GC, Romanha AJ 2004. PCR-RFLP to identify Leishmania (Viannia) braziliensis and L. (Leishmania) amazonensis causing American cutaneous leishmaniasis. Acta Trop, 90, 31-37. Von Stebut EE, J. M.; Belkaid, Y.; Kostka, S. L.; Molle, K.; Knop, J.; Sunderkotter, C.; Udey, M. C. I. 2003. Interleukin 1 alpha promotes Th1 differentiation and inhibits disease progression in Leishmania major-susceptible BALB/c mice. Journal of Experimental Medicine, 198, 191-199. Voronov E, Dotan S, Gayvoronsky L, White RM, Cohen I, Krelin Y, Benchetrit F, Elkabets M, Huszar M, El-On J, Apte RN 2010. IL-1-induced inflammation promotes development of leishmaniasis in susceptible BALB/c mice. Int Immunol, 22, 245-257. Watford WT, Moriguch
dc.rights.driver.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Universidade Federal de Goiás
dc.publisher.program.fl_str_mv Programa de Pós-graduação em Medicina Tropical e Saúde Publica (IPTSP)
dc.publisher.initials.fl_str_mv UFG
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Instituto de Patologia Tropical e Saúde Pública - IPTSP (RG)
publisher.none.fl_str_mv Universidade Federal de Goiás
dc.source.none.fl_str_mv reponame:Repositório Institucional da UFG
instname:Universidade Federal de Goiás (UFG)
instacron:UFG
instname_str Universidade Federal de Goiás (UFG)
instacron_str UFG
institution UFG
reponame_str Repositório Institucional da UFG
collection Repositório Institucional da UFG
bitstream.url.fl_str_mv http://repositorio.bc.ufg.br/tede/bitstreams/a21b9619-d33c-49e5-b238-9796c74e20ee/download
http://repositorio.bc.ufg.br/tede/bitstreams/485cb06b-3667-45a5-85f1-993c70702a91/download
http://repositorio.bc.ufg.br/tede/bitstreams/3c2651b0-2e03-41f1-93bf-11bbb196375f/download
http://repositorio.bc.ufg.br/tede/bitstreams/b759f615-c8fb-4828-9892-13b6d89c53a2/download
http://repositorio.bc.ufg.br/tede/bitstreams/d294c9f5-e50c-4b74-9eaa-0dd553d24122/download
http://repositorio.bc.ufg.br/tede/bitstreams/acea2c49-6f9e-4e29-8e77-2e1f1b1dcc5c/download
http://repositorio.bc.ufg.br/tede/bitstreams/9de6d0ec-6079-4c01-a1e6-82ed5a2ec5f8/download
bitstream.checksum.fl_str_mv bd3efa91386c1718a7f26a329fdcb468
4afdbb8c545fd630ea7db775da747b2f
1e0094e9d8adcf16b18effef4ce7ed83
9da0b6dfac957114c6a7714714b86306
48dd1bd05f0e954a3dd14fb20b162e2f
b89fdef7cd297855769f9f44eebb6c5b
632a8af04dc05b92e51373c484153bb6
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositório Institucional da UFG - Universidade Federal de Goiás (UFG)
repository.mail.fl_str_mv tasesdissertacoes.bc@ufg.br
_version_ 1815172526599307264

Registros relacionados