BALB/c mice infected with antimony treatment refractory isolate of Leishmania braziliensis present severe lesions due to IL-4 production
Autor(a) principal: | |
---|---|
Data de Publicação: | 2011 |
Outros Autores: | , , , , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UFS |
Texto Completo: | https://ri.ufs.br/handle/riufs/921 |
Resumo: | BACKGROUND: Leishmania braziliensis is the main causative agent of cutaneous leishmaniasis in Brazil. Protection against infection is related to development of Th1 responses, but the mechanisms that mediate susceptibility are still poorly understood. Murine models have been the most important tools in understanding the immunopathogenesis of L. major infection and have shown that Th2 responses favor parasite survival. In contrast, L. braziliensis–infected mice develop strong Th1 responses and easily resolve the infection, thus making the study of factors affecting susceptibility to this parasite difficult. METHODOLOGY/PRINCIPAL FINDINGS: Here, we describe an experimental model for the evaluation of the mechanisms mediating susceptibility to L. braziliensis infection. BALB/c mice were inoculated with stationary phase promastigotes of L. braziliensis, isolates LTCP393(R) and LTCP15171(S), which are resistant and susceptible to antimony and nitric oxide (NO), respectively. Mice inoculated with LTCP393(R) presented larger lesions that healed more slowly and contained higher parasite loads than lesions caused by LTCP15171(S). Inflammatory infiltrates in the lesions and production of IFN-γ, TNF-α, IL-10 and TGF-β were similar in mice inoculated with either isolate, indicating that these factors did not contribute to the different disease manifestations observed. In contrast, IL-4 production was strongly increased in LTCP393(R)-inoculated animals and also arginase I (Arg I) expression. Moreover, anti-IL-4 monoclonal antibody (mAb) treatment resulted in decreased lesion thickness and parasite burden in animals inoculated with LTCP393(R), but not in those inoculated with LTCP15171(S). CONCLUSION/SIGNIFICANCE: We conclude that the ability of L. braziliensis isolates to induce Th2 responses affects the susceptibility to infection with these isolates and contributes to the increased virulence and severity of disease associated with them. Since these data reflect what happens in human infection, this model could be useful to study the pathogenesis of the L. braziliensis infection, as well as to design new strategies of therapeutic intervention. |
id |
UFS-2_d7aaa547f91ad7373a68f181fddad79b |
---|---|
oai_identifier_str |
oai:ufs.br:riufs/921 |
network_acronym_str |
UFS-2 |
network_name_str |
Repositório Institucional da UFS |
repository_id_str |
|
spelling |
Costa, Diego LuisCarregaro, VanessaLima Júnior, Djalma Souza deSilva, Neide Maria daMilanezi, Cristiane MariaCardoso, Cristina Ribeiro de BarrosGiudice, ÂngelaJesus, Amélia Maria Ribeiro deCarvalho Filho, Edgar Marcelino deAlmeida, Roque Pacheco deSilva, João Santana da2014-02-19T23:51:24Z2014-02-19T23:51:24Z2011-02COSTA, D. L. et al. BALB/c mice infected with antimony treatment refractory isolate of Leishmania braziliensis present severe lesions due to IL-4 production. PLOS Neglected Tropical Diseases, San Francisco, v. 5, n. 3, fev. 2011. Disponível em: <http://www.plosntds.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pntd.0000965&representation=PDF>. Acesso em: 19 fev. 2014.1935-2735https://ri.ufs.br/handle/riufs/921Creative Commons Attribution LicenseBACKGROUND: Leishmania braziliensis is the main causative agent of cutaneous leishmaniasis in Brazil. Protection against infection is related to development of Th1 responses, but the mechanisms that mediate susceptibility are still poorly understood. Murine models have been the most important tools in understanding the immunopathogenesis of L. major infection and have shown that Th2 responses favor parasite survival. In contrast, L. braziliensis–infected mice develop strong Th1 responses and easily resolve the infection, thus making the study of factors affecting susceptibility to this parasite difficult. METHODOLOGY/PRINCIPAL FINDINGS: Here, we describe an experimental model for the evaluation of the mechanisms mediating susceptibility to L. braziliensis infection. BALB/c mice were inoculated with stationary phase promastigotes of L. braziliensis, isolates LTCP393(R) and LTCP15171(S), which are resistant and susceptible to antimony and nitric oxide (NO), respectively. Mice inoculated with LTCP393(R) presented larger lesions that healed more slowly and contained higher parasite loads than lesions caused by LTCP15171(S). Inflammatory infiltrates in the lesions and production of IFN-γ, TNF-α, IL-10 and TGF-β were similar in mice inoculated with either isolate, indicating that these factors did not contribute to the different disease manifestations observed. In contrast, IL-4 production was strongly increased in LTCP393(R)-inoculated animals and also arginase I (Arg I) expression. Moreover, anti-IL-4 monoclonal antibody (mAb) treatment resulted in decreased lesion thickness and parasite burden in animals inoculated with LTCP393(R), but not in those inoculated with LTCP15171(S). CONCLUSION/SIGNIFICANCE: We conclude that the ability of L. braziliensis isolates to induce Th2 responses affects the susceptibility to infection with these isolates and contributes to the increased virulence and severity of disease associated with them. Since these data reflect what happens in human infection, this model could be useful to study the pathogenesis of the L. braziliensis infection, as well as to design new strategies of therapeutic intervention.This study was supported by the Brazilian National Research Council (CNPq) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP). JSS, EMC, ARJ and RPA are investigators from the Brazilian National Research Council (CNPq). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Public Library of ScienceLeishmaniaLeishmania braziliensisLeishmanioseImunopatogêneseBALB/c mice infected with antimony treatment refractory isolate of Leishmania braziliensis present severe lesions due to IL-4 productioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleengreponame:Repositório Institucional da UFSinstname:Universidade Federal de Sergipe (UFS)instacron:UFSinfo:eu-repo/semantics/openAccessTHUMBNAILBALBMice Leishmania.pdf.jpgBALBMice Leishmania.pdf.jpgGenerated Thumbnailimage/jpeg1877https://ri.ufs.br/jspui/bitstream/riufs/921/4/BALBMice%20Leishmania.pdf.jpgb8d5e3096331dd116ee60c36d843cf6eMD54ORIGINALBALBMice Leishmania.pdfBALBMice Leishmania.pdfapplication/pdf1195014https://ri.ufs.br/jspui/bitstream/riufs/921/1/BALBMice%20Leishmania.pdf45a6b7a8b497298ceeee12ff00ef2ad8MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://ri.ufs.br/jspui/bitstream/riufs/921/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52TEXTBALBMice Leishmania.pdf.txtBALBMice Leishmania.pdf.txtExtracted texttext/plain64107https://ri.ufs.br/jspui/bitstream/riufs/921/3/BALBMice%20Leishmania.pdf.txt5972348d1ab4bddcac2c6eb0d7fc9f71MD53riufs/9212014-02-20 18:26:42.07oai:ufs.br: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Repositório InstitucionalPUBhttps://ri.ufs.br/oai/requestrepositorio@academico.ufs.bropendoar:2014-02-20T21:26:42Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS)false |
dc.title.pt_BR.fl_str_mv |
BALB/c mice infected with antimony treatment refractory isolate of Leishmania braziliensis present severe lesions due to IL-4 production |
title |
BALB/c mice infected with antimony treatment refractory isolate of Leishmania braziliensis present severe lesions due to IL-4 production |
spellingShingle |
BALB/c mice infected with antimony treatment refractory isolate of Leishmania braziliensis present severe lesions due to IL-4 production Costa, Diego Luis Leishmania Leishmania braziliensis Leishmaniose Imunopatogênese |
title_short |
BALB/c mice infected with antimony treatment refractory isolate of Leishmania braziliensis present severe lesions due to IL-4 production |
title_full |
BALB/c mice infected with antimony treatment refractory isolate of Leishmania braziliensis present severe lesions due to IL-4 production |
title_fullStr |
BALB/c mice infected with antimony treatment refractory isolate of Leishmania braziliensis present severe lesions due to IL-4 production |
title_full_unstemmed |
BALB/c mice infected with antimony treatment refractory isolate of Leishmania braziliensis present severe lesions due to IL-4 production |
title_sort |
BALB/c mice infected with antimony treatment refractory isolate of Leishmania braziliensis present severe lesions due to IL-4 production |
author |
Costa, Diego Luis |
author_facet |
Costa, Diego Luis Carregaro, Vanessa Lima Júnior, Djalma Souza de Silva, Neide Maria da Milanezi, Cristiane Maria Cardoso, Cristina Ribeiro de Barros Giudice, Ângela Jesus, Amélia Maria Ribeiro de Carvalho Filho, Edgar Marcelino de Almeida, Roque Pacheco de Silva, João Santana da |
author_role |
author |
author2 |
Carregaro, Vanessa Lima Júnior, Djalma Souza de Silva, Neide Maria da Milanezi, Cristiane Maria Cardoso, Cristina Ribeiro de Barros Giudice, Ângela Jesus, Amélia Maria Ribeiro de Carvalho Filho, Edgar Marcelino de Almeida, Roque Pacheco de Silva, João Santana da |
author2_role |
author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Costa, Diego Luis Carregaro, Vanessa Lima Júnior, Djalma Souza de Silva, Neide Maria da Milanezi, Cristiane Maria Cardoso, Cristina Ribeiro de Barros Giudice, Ângela Jesus, Amélia Maria Ribeiro de Carvalho Filho, Edgar Marcelino de Almeida, Roque Pacheco de Silva, João Santana da |
dc.subject.por.fl_str_mv |
Leishmania Leishmania braziliensis Leishmaniose Imunopatogênese |
topic |
Leishmania Leishmania braziliensis Leishmaniose Imunopatogênese |
description |
BACKGROUND: Leishmania braziliensis is the main causative agent of cutaneous leishmaniasis in Brazil. Protection against infection is related to development of Th1 responses, but the mechanisms that mediate susceptibility are still poorly understood. Murine models have been the most important tools in understanding the immunopathogenesis of L. major infection and have shown that Th2 responses favor parasite survival. In contrast, L. braziliensis–infected mice develop strong Th1 responses and easily resolve the infection, thus making the study of factors affecting susceptibility to this parasite difficult. METHODOLOGY/PRINCIPAL FINDINGS: Here, we describe an experimental model for the evaluation of the mechanisms mediating susceptibility to L. braziliensis infection. BALB/c mice were inoculated with stationary phase promastigotes of L. braziliensis, isolates LTCP393(R) and LTCP15171(S), which are resistant and susceptible to antimony and nitric oxide (NO), respectively. Mice inoculated with LTCP393(R) presented larger lesions that healed more slowly and contained higher parasite loads than lesions caused by LTCP15171(S). Inflammatory infiltrates in the lesions and production of IFN-γ, TNF-α, IL-10 and TGF-β were similar in mice inoculated with either isolate, indicating that these factors did not contribute to the different disease manifestations observed. In contrast, IL-4 production was strongly increased in LTCP393(R)-inoculated animals and also arginase I (Arg I) expression. Moreover, anti-IL-4 monoclonal antibody (mAb) treatment resulted in decreased lesion thickness and parasite burden in animals inoculated with LTCP393(R), but not in those inoculated with LTCP15171(S). CONCLUSION/SIGNIFICANCE: We conclude that the ability of L. braziliensis isolates to induce Th2 responses affects the susceptibility to infection with these isolates and contributes to the increased virulence and severity of disease associated with them. Since these data reflect what happens in human infection, this model could be useful to study the pathogenesis of the L. braziliensis infection, as well as to design new strategies of therapeutic intervention. |
publishDate |
2011 |
dc.date.issued.fl_str_mv |
2011-02 |
dc.date.accessioned.fl_str_mv |
2014-02-19T23:51:24Z |
dc.date.available.fl_str_mv |
2014-02-19T23:51:24Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
COSTA, D. L. et al. BALB/c mice infected with antimony treatment refractory isolate of Leishmania braziliensis present severe lesions due to IL-4 production. PLOS Neglected Tropical Diseases, San Francisco, v. 5, n. 3, fev. 2011. Disponível em: <http://www.plosntds.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pntd.0000965&representation=PDF>. Acesso em: 19 fev. 2014. |
dc.identifier.uri.fl_str_mv |
https://ri.ufs.br/handle/riufs/921 |
dc.identifier.issn.none.fl_str_mv |
1935-2735 |
dc.identifier.license.pt_BR.fl_str_mv |
Creative Commons Attribution License |
identifier_str_mv |
COSTA, D. L. et al. BALB/c mice infected with antimony treatment refractory isolate of Leishmania braziliensis present severe lesions due to IL-4 production. PLOS Neglected Tropical Diseases, San Francisco, v. 5, n. 3, fev. 2011. Disponível em: <http://www.plosntds.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pntd.0000965&representation=PDF>. Acesso em: 19 fev. 2014. 1935-2735 Creative Commons Attribution License |
url |
https://ri.ufs.br/handle/riufs/921 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Public Library of Science |
publisher.none.fl_str_mv |
Public Library of Science |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFS instname:Universidade Federal de Sergipe (UFS) instacron:UFS |
instname_str |
Universidade Federal de Sergipe (UFS) |
instacron_str |
UFS |
institution |
UFS |
reponame_str |
Repositório Institucional da UFS |
collection |
Repositório Institucional da UFS |
bitstream.url.fl_str_mv |
https://ri.ufs.br/jspui/bitstream/riufs/921/4/BALBMice%20Leishmania.pdf.jpg https://ri.ufs.br/jspui/bitstream/riufs/921/1/BALBMice%20Leishmania.pdf https://ri.ufs.br/jspui/bitstream/riufs/921/2/license.txt https://ri.ufs.br/jspui/bitstream/riufs/921/3/BALBMice%20Leishmania.pdf.txt |
bitstream.checksum.fl_str_mv |
b8d5e3096331dd116ee60c36d843cf6e 45a6b7a8b497298ceeee12ff00ef2ad8 8a4605be74aa9ea9d79846c1fba20a33 5972348d1ab4bddcac2c6eb0d7fc9f71 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 MD5 MD5 |
repository.name.fl_str_mv |
Repositório Institucional da UFS - Universidade Federal de Sergipe (UFS) |
repository.mail.fl_str_mv |
repositorio@academico.ufs.br |
_version_ |
1802110808647270400 |