Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2013 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/20770 |
Resumo: | National Institutes of Health: (RO176257, http://grants.nih.gov/grants/oer.htm); International Centers for Infectious Disease Research grant (U01- AUI 088650), Conselho Nacional de Desenvolvimento CientÍfico e TecnolÓgico (CNPq) |
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Novais, Fernanda OliveiraCarvalho, Lucas Pedreira deGraff, Joel WBeiting, Daniel PRuthel, GordonRoos, David SBetts, Michael RGoldschmidt, Michael HWilson, Mary EOliveira, Camila Indiani deScott, Phillip2017-08-25T17:01:37Z2017-08-25T17:01:37Z2013NOVAIS, F. O. et al. Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis. Plos Pathogens, v. 9, n. 7 p. e1003504, 2013.1553-7366https://www.arca.fiocruz.br/handle/icict/2077010.1371/journal.ppat.1003504National Institutes of Health: (RO176257, http://grants.nih.gov/grants/oer.htm); International Centers for Infectious Disease Research grant (U01- AUI 088650), Conselho Nacional de Desenvolvimento CientÍfico e TecnolÓgico (CNPq)University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USAUniversidade Federal da Bahia. Hospital Universitario Prof. Edgard Santos. Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais. Serviço de Imunologia. Salvador, BA, BrasilUniversity of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USAUniversity of Pennsylvania. Department of Biology. Philadelphia Pennsylvania, USAUniversity of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USAUniversity of Pennsylvania. Department of Biology. Philadelphia Pennsylvania, USAUniversity of Pennsylvania. Perelman School of Medicine. Department of Microbiology. Philadelphia, Pennsylvania, USAUniversity of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USAUniversity of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USAFundação Gonçalo Moniz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversity of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USADisease 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.engPublic Library of ScienceLeishmaniose CutâneaLeishmania braziliensisCitotoxicidade imunológicaLinfócitos T CitotóxicosRatosLeishmaniasis, CutaneousLeishmania braziliensisCytotoxicity, ImmunologicT-Lymphocytes, CytotoxicMiceCytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/20770/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALNovais FO Cytotoxic T cells ....pdfNovais FO Cytotoxic T cells 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| dc.title.pt_BR.fl_str_mv |
Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis |
| title |
Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis |
| spellingShingle |
Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis Novais, Fernanda Oliveira Leishmaniose Cutânea Leishmania braziliensis Citotoxicidade imunológica Linfócitos T Citotóxicos Ratos Leishmaniasis, Cutaneous Leishmania braziliensis Cytotoxicity, Immunologic T-Lymphocytes, Cytotoxic Mice |
| 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 Oliveira |
| author_facet |
Novais, Fernanda Oliveira 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 Oliveira 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.other.pt_BR.fl_str_mv |
Leishmaniose Cutânea Leishmania braziliensis Citotoxicidade imunológica Linfócitos T Citotóxicos Ratos |
| topic |
Leishmaniose Cutânea Leishmania braziliensis Citotoxicidade imunológica Linfócitos T Citotóxicos Ratos Leishmaniasis, Cutaneous Leishmania braziliensis Cytotoxicity, Immunologic T-Lymphocytes, Cytotoxic Mice |
| dc.subject.en.pt_BR.fl_str_mv |
Leishmaniasis, Cutaneous Leishmania braziliensis Cytotoxicity, Immunologic T-Lymphocytes, Cytotoxic Mice |
| description |
National Institutes of Health: (RO176257, http://grants.nih.gov/grants/oer.htm); International Centers for Infectious Disease Research grant (U01- AUI 088650), Conselho Nacional de Desenvolvimento CientÍfico e TecnolÓgico (CNPq) |
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2013 |
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2013 |
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2017-08-25T17:01:37Z |
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2017-08-25T17:01:37Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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NOVAIS, F. O. et al. Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis. Plos Pathogens, v. 9, n. 7 p. e1003504, 2013. |
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https://www.arca.fiocruz.br/handle/icict/20770 |
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1553-7366 |
| dc.identifier.doi.none.fl_str_mv |
10.1371/journal.ppat.1003504 |
| identifier_str_mv |
NOVAIS, F. O. et al. Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis. Plos Pathogens, v. 9, n. 7 p. e1003504, 2013. 1553-7366 10.1371/journal.ppat.1003504 |
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