Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis

Detalhes bibliográficos
Autor(a) principal: Novais, Fernanda O.
Data de Publicação: 2013
Outros Autores: Carvalho, Lucas Pedreira de, Graff, Joel W., Beiting, Daniel P., Ruthel, Gordon, Roos, David S., Betts, Michael R., Goldschmidt, Michael H., Wilson, Mary E., Oliveira, Camila Indiani de, Scott, Phillip
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UFBA
Texto Completo: http://repositorio.ufba.br/ri/handle/ri/15015
Resumo: p. 1-11
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spelling Novais, Fernanda O.Carvalho, Lucas Pedreira deGraff, Joel W.Beiting, Daniel P.Ruthel, GordonRoos, David S.Betts, Michael R.Goldschmidt, Michael H.Wilson, Mary E.Oliveira, Camila Indiani deScott, Phillip2014-05-26T13:45:57Z2014-05-26T13:45:57Z20131553-7366http://repositorio.ufba.br/ri/handle/ri/15015v. 9, n. 7p. 1-11Disease progression in response to infection can be strongly influenced by both pathogen burden and infection-induced immunopathology. While current therapeutics focus on augmenting protective immune responses, identifying therapeutics that reduce infection-induced immunopathology are clearly warranted. Despite the apparent protective role for murine CD8+ T cells following infection with the intracellular parasite Leishmania, CD8+ T cells have been paradoxically linked to immunopathological responses in human cutaneous leishmaniasis. Transcriptome analysis of lesions from Leishmania braziliensis patients revealed that genes associated with the cytolytic pathway are highly expressed and CD8+ T cells from lesions exhibited a cytolytic phenotype. To determine if CD8+ T cells play a causal role in disease, we turned to a murine model. These studies revealed that disease progression and metastasis in L. braziliensis infected mice was independent of parasite burden and was instead directly associated with the presence of CD8+ T cells. In mice with severe pathology, we visualized CD8+ T cell degranulation and lysis of L. braziliensis infected cells. Finally, in contrast to wild-type CD8+ T cells, perforin-deficient cells failed to induce disease. Thus, we show for the first time that cytolytic CD8+ T cells mediate immunopathology and drive the development of metastatic lesions in cutaneous leishmaniasis.Submitted by Suelen Reis (suziy.ellen@gmail.com) on 2014-05-20T14:50:08Z No. of bitstreams: 1 10.1371-journal.ppat.1003504.pdf: 1217813 bytes, checksum: 9fcc505b5db15908f14a41556227d1fd (MD5)Approved for entry into archive by Alda Lima da Silva (sivalda@ufba.br) on 2014-05-26T13:45:57Z (GMT) No. of bitstreams: 1 10.1371-journal.ppat.1003504.pdf: 1217813 bytes, checksum: 9fcc505b5db15908f14a41556227d1fd (MD5)Made available in DSpace on 2014-05-26T13:45:57Z (GMT). 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dc.title.pt_BR.fl_str_mv Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis
dc.title.alternative.pt_BR.fl_str_mv PLoS Pathogens
title Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis
spellingShingle Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis
Novais, Fernanda O.
Imunopatologia
Leishmaniose cutânea
title_short Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis
title_full Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis
title_fullStr Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis
title_full_unstemmed Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis
title_sort Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis
author Novais, Fernanda O.
author_facet Novais, Fernanda O.
Carvalho, Lucas Pedreira de
Graff, Joel W.
Beiting, Daniel P.
Ruthel, Gordon
Roos, David S.
Betts, Michael R.
Goldschmidt, Michael H.
Wilson, Mary E.
Oliveira, Camila Indiani de
Scott, Phillip
author_role author
author2 Carvalho, Lucas Pedreira de
Graff, Joel W.
Beiting, Daniel P.
Ruthel, Gordon
Roos, David S.
Betts, Michael R.
Goldschmidt, Michael H.
Wilson, Mary E.
Oliveira, Camila Indiani de
Scott, Phillip
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Novais, Fernanda O.
Carvalho, Lucas Pedreira de
Graff, Joel W.
Beiting, Daniel P.
Ruthel, Gordon
Roos, David S.
Betts, Michael R.
Goldschmidt, Michael H.
Wilson, Mary E.
Oliveira, Camila Indiani de
Scott, Phillip
dc.subject.por.fl_str_mv Imunopatologia
Leishmaniose cutânea
topic Imunopatologia
Leishmaniose cutânea
description p. 1-11
publishDate 2013
dc.date.issued.fl_str_mv 2013
dc.date.accessioned.fl_str_mv 2014-05-26T13:45:57Z
dc.date.available.fl_str_mv 2014-05-26T13:45:57Z
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dc.identifier.uri.fl_str_mv http://repositorio.ufba.br/ri/handle/ri/15015
dc.identifier.issn.none.fl_str_mv 1553-7366
dc.identifier.number.pt_BR.fl_str_mv v. 9, n. 7
identifier_str_mv 1553-7366
v. 9, n. 7
url http://repositorio.ufba.br/ri/handle/ri/15015
dc.language.iso.fl_str_mv eng
language eng
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dc.publisher.country.fl_str_mv Brasil
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