Author | Novais, Fernanda Oliveira | |
Author | Carvalho, Lucas Pedreira de | |
Author | Graff, Joel W | |
Author | Beiting, Daniel P | |
Author | Ruthel, Gordon | |
Author | Roos, David S | |
Author | Betts, Michael R | |
Author | Goldschmidt, Michael H | |
Author | Wilson, Mary E | |
Author | Oliveira, Camila Indiani de | |
Author | Scott, Phillip | |
Access date | 2017-08-25T17:01:37Z | |
Available date | 2017-08-25T17:01:37Z | |
Document date | 2013 | |
Citation | NOVAIS, F. O. et al. Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis. Plos Pathogens, v. 9, n. 7 p. e1003504, 2013. | pt_BR |
ISSN | 1553-7366 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/20770 | |
Sponsorship | 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) | pt_BR |
Language | eng | pt_BR |
Publisher | Public Library of Science | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Leishmaniose Cutânea | pt_BR |
Subject in Portuguese | Leishmania braziliensis | pt_BR |
Subject in Portuguese | Citotoxicidade imunológica | pt_BR |
Subject in Portuguese | Linfócitos T Citotóxicos | pt_BR |
Subject in Portuguese | Ratos | pt_BR |
Title | Cytotoxic T cells mediate pathology and metastasis in cutaneous leishmaniasis | pt_BR |
Type | Article | pt_BR |
DOI | 10.1371/journal.ppat.1003504 | |
Abstract | Disease 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. | pt_BR |
Affilliation | University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA | pt_BR |
Affilliation | Universidade Federal da Bahia. Hospital Universitario Prof. Edgard Santos. Instituto Nacional de Ciência e Tecnologia de Doenças Tropicais. Serviço de Imunologia. Salvador, BA, Brasil | pt_BR |
Affilliation | University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA | pt_BR |
Affilliation | University of Pennsylvania. Department of Biology. Philadelphia Pennsylvania, USA | pt_BR |
Affilliation | University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA | pt_BR |
Affilliation | University of Pennsylvania. Department of Biology. Philadelphia Pennsylvania, USA | pt_BR |
Affilliation | University of Pennsylvania. Perelman School of Medicine. Department of Microbiology. Philadelphia, Pennsylvania, USA | pt_BR |
Affilliation | University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA | pt_BR |
Affilliation | University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA | pt_BR |
Affilliation | Fundação Gonçalo Moniz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil | pt_BR |
Affilliation | University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA | pt_BR |
Subject | Leishmaniasis, Cutaneous | pt_BR |
Subject | Leishmania braziliensis | pt_BR |
Subject | Cytotoxicity, Immunologic | pt_BR |
Subject | T-Lymphocytes, Cytotoxic | pt_BR |
Subject | Mice | pt_BR |