Modulação da resposta celular e da via de sinalização do IFN-γ pela Glucuronoxilomanana (GXM) de Cryptococcus neoformans

Detalhes bibliográficos
Autor(a) principal: ARAÚJO, Alessandra da Silva
Data de Publicação: 2015
Tipo de documento: Dissertação
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFTM
Texto Completo: http://bdtd.uftm.edu.br/handle/tede/394
Resumo: A criptococose é uma micose sistêmica causada por Cryptococcus neoformans e Cryptococcus gattii, leveduras capsuladas, que acometem principalmente indivíduos imunocomprometidos e imunocompetentes, respectivamente. A infecção ocorre após a inalação de propágulos do microrganismo dispersos no ar, que posteriormente penetram nos pulmões, com tendência para invadir o sistema nervoso central (SNC). A cápsula polissacarídica é o principal fator de virulência desse fungo, composta majoritariamente por glucuronoxilomanana (GXM), componente de superfície mais externo, com grande potencial imunogênico que parece ser fundamental na proteção desses fungos contra as defesas do hospedeiro. Neste trabalho avaliamos os efeitos imunoregulatórios da GXM obtida do C. neoformans sobre a resposta de células polimorfonucleares (PMN) e mononucleares humanas de sangue periférico (PBMC) ao IFN-γ recombinante. No primeiro momento avaliamos o efeito da GXM sobre a produção de CXCL10 após estimulação com IFN-γ no sobrenadante de cultura celular, e em seguida investigamos intracelularmente em PMN e PBMC a produção desta quimiocina através de citometria de fluxo. Os resultados mostraram que a GXM possui capacidade de modular a resposta de PMN e PBMC ao IFN-γ, através da diminuição na produção de CXCL10. Posteriormente, avaliamos a expressão do receptor do IFN-γ (IFN- γR1/CD119) por citometria de fluxo. Os dados obtidos mostram que a GXM modula negativamente a expressão desse receptor. Por fim, monócitos humanos apresentaram redução significativa na fosforilação de STAT1 após pré-tratamento in vitro com GXM. Deste modo, nosso estudo demonstrou que a GXM de C. neoformans interfere na modulação da resposta ao IFN-γ e na sua via de sinalização em PMN e PBMC. Os resultados obtidos no presente estudo auxiliam no entendimento dos mecanismos patogênicos utilizados pelo C. neoformans na evasão do sistema imune, podendo contribuir para o desenvolvimento de novas estratégias terapêuticas para a criptococose.
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spelling Modulação da resposta celular e da via de sinalização do IFN-γ pela Glucuronoxilomanana (GXM) de Cryptococcus neoformansCryptococcus.Glucuronoxilomanana (GXM).CXCL10.IFN-γR1.STAT1.Cryptococcus.Glucuronoxilomanan (GXM).CXCL10.IFN-γR1.STAT1.Ciências BiológicasA criptococose é uma micose sistêmica causada por Cryptococcus neoformans e Cryptococcus gattii, leveduras capsuladas, que acometem principalmente indivíduos imunocomprometidos e imunocompetentes, respectivamente. A infecção ocorre após a inalação de propágulos do microrganismo dispersos no ar, que posteriormente penetram nos pulmões, com tendência para invadir o sistema nervoso central (SNC). A cápsula polissacarídica é o principal fator de virulência desse fungo, composta majoritariamente por glucuronoxilomanana (GXM), componente de superfície mais externo, com grande potencial imunogênico que parece ser fundamental na proteção desses fungos contra as defesas do hospedeiro. Neste trabalho avaliamos os efeitos imunoregulatórios da GXM obtida do C. neoformans sobre a resposta de células polimorfonucleares (PMN) e mononucleares humanas de sangue periférico (PBMC) ao IFN-γ recombinante. No primeiro momento avaliamos o efeito da GXM sobre a produção de CXCL10 após estimulação com IFN-γ no sobrenadante de cultura celular, e em seguida investigamos intracelularmente em PMN e PBMC a produção desta quimiocina através de citometria de fluxo. Os resultados mostraram que a GXM possui capacidade de modular a resposta de PMN e PBMC ao IFN-γ, através da diminuição na produção de CXCL10. Posteriormente, avaliamos a expressão do receptor do IFN-γ (IFN- γR1/CD119) por citometria de fluxo. Os dados obtidos mostram que a GXM modula negativamente a expressão desse receptor. Por fim, monócitos humanos apresentaram redução significativa na fosforilação de STAT1 após pré-tratamento in vitro com GXM. Deste modo, nosso estudo demonstrou que a GXM de C. neoformans interfere na modulação da resposta ao IFN-γ e na sua via de sinalização em PMN e PBMC. Os resultados obtidos no presente estudo auxiliam no entendimento dos mecanismos patogênicos utilizados pelo C. neoformans na evasão do sistema imune, podendo contribuir para o desenvolvimento de novas estratégias terapêuticas para a criptococose.Cryptococcosis is an systemic fungal infection caused by Cryptococcus neoformans and Cryptococcus gattii, encapsulated yeasts, affecting mainly immunocompromised and immunocompetent individuals respectively. Infection occurs after inhalation of microorganism’s propagules dispersed in the air, which subsequently penetrates into the lungs, with a tendency to invade the central nervous system. The polysaccharide capsule is the main virulence factor of this fungus, composed mostly of glucuronoxilomanan (GXM), an outer surface component, with great immunogenic potential that appears to be essential in protecting these fungi against host defenses. In this work we evaluate the immunoregulatory effects of GXM obtained from C. neoformans on polymorphonuclear (PMN) and peripheral blood human mononuclear cell (PBMC) response to recombinant human IFN-γ. Initially, we evaluated the effect of GXM on CXCL10 production in cell culture supernatants and subsequently, the intracellular chemokine production in PMNs and PBMCs by flow cytometry. The results showed that GXM modulates PMN and PBMC response to IFN-γ by reducing CXCL10 production. The evaluation of IFN-γ receptor alpha chain (IFN- γR1/CD119) expression by flow cytometry revealed that GXM reduces the expression of this receptor. Finally, human monocytes significantly reduced STAT1 phosphorylation after in vitro incubation with GXM. Thus, our study demonstrated that GXM from C. neoformans interferes with cellular response to IFN-γ and its signaling pathways in human PMN and PBMC. The data obtained in the present study increases the understanding of pathogenic mechanisms used by C. neoformans to escape host’s immune system, and may contribute to development of new therapeutic strategies for cryptococosis.Universidade Federal do Triângulo MineiroInstituto de Ciências da Saúde - ICS::Curso de MedicinaBrasilUFTMCurso de Pós-Graduação em Ciências Fisiológicas - Parasitologia, Imunologia e MicrobiologiaTEIXEIRA, David Nascimento Silva58032762604http://lattes.cnpq.br/3854191631282492ARAÚJO, Alessandra da Silva2017-08-10T22:07:39Z2015-05-29info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfapplication/pdfARAÚJO, Alessandra da Silva. 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R.; MURPHY, W. J. Protection from direct cerebral Cryptococcus infection by interferon-gamma-dependent activation of microglial cells. J Immunol, v. 178, p. 5753-5761, 2007.http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da UFTMinstname:Universidade Federal do Triangulo Mineiro (UFTM)instacron:UFTM2019-06-26T19:17:20Zoai:bdtd.uftm.edu.br:tede/394Biblioteca Digital de Teses e Dissertaçõeshttp://bdtd.uftm.edu.br/PUBhttp://bdtd.uftm.edu.br/oai/requestbdtd@uftm.edu.br||bdtd@uftm.edu.bropendoar:2019-06-26T19:17:20Biblioteca Digital de Teses e Dissertações da UFTM - Universidade Federal do Triangulo Mineiro (UFTM)false
dc.title.none.fl_str_mv Modulação da resposta celular e da via de sinalização do IFN-γ pela Glucuronoxilomanana (GXM) de Cryptococcus neoformans
title Modulação da resposta celular e da via de sinalização do IFN-γ pela Glucuronoxilomanana (GXM) de Cryptococcus neoformans
spellingShingle Modulação da resposta celular e da via de sinalização do IFN-γ pela Glucuronoxilomanana (GXM) de Cryptococcus neoformans
ARAÚJO, Alessandra da Silva
Cryptococcus.
Glucuronoxilomanana (GXM).
CXCL10.
IFN-γR1.
STAT1.
Cryptococcus.
Glucuronoxilomanan (GXM).
CXCL10.
IFN-γR1.
STAT1.
Ciências Biológicas
title_short Modulação da resposta celular e da via de sinalização do IFN-γ pela Glucuronoxilomanana (GXM) de Cryptococcus neoformans
title_full Modulação da resposta celular e da via de sinalização do IFN-γ pela Glucuronoxilomanana (GXM) de Cryptococcus neoformans
title_fullStr Modulação da resposta celular e da via de sinalização do IFN-γ pela Glucuronoxilomanana (GXM) de Cryptococcus neoformans
title_full_unstemmed Modulação da resposta celular e da via de sinalização do IFN-γ pela Glucuronoxilomanana (GXM) de Cryptococcus neoformans
title_sort Modulação da resposta celular e da via de sinalização do IFN-γ pela Glucuronoxilomanana (GXM) de Cryptococcus neoformans
author ARAÚJO, Alessandra da Silva
author_facet ARAÚJO, Alessandra da Silva
author_role author
dc.contributor.none.fl_str_mv TEIXEIRA, David Nascimento Silva
58032762604
http://lattes.cnpq.br/3854191631282492
dc.contributor.author.fl_str_mv ARAÚJO, Alessandra da Silva
dc.subject.por.fl_str_mv Cryptococcus.
Glucuronoxilomanana (GXM).
CXCL10.
IFN-γR1.
STAT1.
Cryptococcus.
Glucuronoxilomanan (GXM).
CXCL10.
IFN-γR1.
STAT1.
Ciências Biológicas
topic Cryptococcus.
Glucuronoxilomanana (GXM).
CXCL10.
IFN-γR1.
STAT1.
Cryptococcus.
Glucuronoxilomanan (GXM).
CXCL10.
IFN-γR1.
STAT1.
Ciências Biológicas
description A criptococose é uma micose sistêmica causada por Cryptococcus neoformans e Cryptococcus gattii, leveduras capsuladas, que acometem principalmente indivíduos imunocomprometidos e imunocompetentes, respectivamente. A infecção ocorre após a inalação de propágulos do microrganismo dispersos no ar, que posteriormente penetram nos pulmões, com tendência para invadir o sistema nervoso central (SNC). A cápsula polissacarídica é o principal fator de virulência desse fungo, composta majoritariamente por glucuronoxilomanana (GXM), componente de superfície mais externo, com grande potencial imunogênico que parece ser fundamental na proteção desses fungos contra as defesas do hospedeiro. Neste trabalho avaliamos os efeitos imunoregulatórios da GXM obtida do C. neoformans sobre a resposta de células polimorfonucleares (PMN) e mononucleares humanas de sangue periférico (PBMC) ao IFN-γ recombinante. No primeiro momento avaliamos o efeito da GXM sobre a produção de CXCL10 após estimulação com IFN-γ no sobrenadante de cultura celular, e em seguida investigamos intracelularmente em PMN e PBMC a produção desta quimiocina através de citometria de fluxo. Os resultados mostraram que a GXM possui capacidade de modular a resposta de PMN e PBMC ao IFN-γ, através da diminuição na produção de CXCL10. Posteriormente, avaliamos a expressão do receptor do IFN-γ (IFN- γR1/CD119) por citometria de fluxo. Os dados obtidos mostram que a GXM modula negativamente a expressão desse receptor. Por fim, monócitos humanos apresentaram redução significativa na fosforilação de STAT1 após pré-tratamento in vitro com GXM. Deste modo, nosso estudo demonstrou que a GXM de C. neoformans interfere na modulação da resposta ao IFN-γ e na sua via de sinalização em PMN e PBMC. Os resultados obtidos no presente estudo auxiliam no entendimento dos mecanismos patogênicos utilizados pelo C. neoformans na evasão do sistema imune, podendo contribuir para o desenvolvimento de novas estratégias terapêuticas para a criptococose.
publishDate 2015
dc.date.none.fl_str_mv 2015-05-29
2017-08-10T22:07:39Z
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.uri.fl_str_mv ARAÚJO, Alessandra da Silva. Modulação da resposta celular e da via de sinalização do IFN-γ pela Glucuronoxilomanana (GXM) de Cryptococcus neoformans. 2015. 96f. Dissertação (Mestrado em Ciências Fisiológicas) - Programa de Pós-Graduação em Ciências Fisiológicas, Universidade Federal do Triângulo Mineiro, Uberaba, 2015.
http://bdtd.uftm.edu.br/handle/tede/394
identifier_str_mv ARAÚJO, Alessandra da Silva. Modulação da resposta celular e da via de sinalização do IFN-γ pela Glucuronoxilomanana (GXM) de Cryptococcus neoformans. 2015. 96f. Dissertação (Mestrado em Ciências Fisiológicas) - Programa de Pós-Graduação em Ciências Fisiológicas, Universidade Federal do Triângulo Mineiro, Uberaba, 2015.
url http://bdtd.uftm.edu.br/handle/tede/394
dc.language.iso.fl_str_mv por
language por
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G. Comparative analysis of environmental and clinical populations of Cryptococcus neoformans. J Clin Microbiol., v.43, n.2, p.556-64, 2005. LIU, M.; GUO, S.; HIBBERT, J. M. .; JAIN, V.; SINGH, N.; WILSON, N. O.; STILES, J. K. CXCL10/IP-10 in infectious diseases pathogenesis and potential therapeutic implications. Cytokine and Growth Factor Reviews, v. 22, n. 3, p. 121-130, 2011. LIU, P.Y.; YANG, Y.; SHI, Z.-Y. Cryptococcal liver abscess: a case report of successful treatment with amphotericin-B and literature review. Japanese journal of infectious diseases, v. 62, p. 59-60, 2009. LIU, T.; PERLIN, D. S.; XUE, C. Molecular mechanisms of cryptococcal meningitis. Virulence, v. 3, p. 173-181, 2012. LIU, X.; LING, Z.; LI, L.; RUAN, B. Invasive fungal infections in liver transplantation. International Journal of Infectious Diseases, v. 15, n. 5, p. e298-e304, 2011.85 LIU, Y.; MA, S.; WANG, X.; XU, W.; TANG, J. 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CXCL10 is required to maintain T-cell populations and to control parasite replication during chronic ocular toxoplasmosis. Investigative Ophthalmology and Visual Science, v. 52, n. 1, p. 389-398, 2011. OLIVEIRA, L.; MARTINS, M. A.; VIDAL, J. E.; SZESZS, M. W.; PAPPALARDO
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dc.publisher.none.fl_str_mv Universidade Federal do Triângulo Mineiro
Instituto de Ciências da Saúde - ICS::Curso de Medicina
Brasil
UFTM
Curso de Pós-Graduação em Ciências Fisiológicas - Parasitologia, Imunologia e Microbiologia
publisher.none.fl_str_mv Universidade Federal do Triângulo Mineiro
Instituto de Ciências da Saúde - ICS::Curso de Medicina
Brasil
UFTM
Curso de Pós-Graduação em Ciências Fisiológicas - Parasitologia, Imunologia e Microbiologia
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