Author | Novais, Fernanda Oliveira | |
Author | Carvalho, Augusto M | |
Author | Clark, Megan L | |
Author | Carvalho, Lucas Pedreira de | |
Author | Beiting, Daniel P | |
Author | Brodsky, Igor E | |
Author | Carvalho Filho, Edgar Marcelino | |
Author | Scott, Phillip | |
Access date | 2018-03-26T16:39:03Z | |
Available date | 2018-03-26T16:39:03Z | |
Document date | 2017 | |
Citation | NOVAIS, F. O. et al. CD8+ T cell cytotoxicity mediates pathology in the skin by inflammasome activation and IL-1β production. Plos Pathogens, v. 13, n. 2, p. e1006196, 2017. | pt_BR |
ISSN | 1553-7366 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/25494 | |
Sponsorship | NIH (R01 AI 106842 and U01 AI088650-06 to PS; P50 AI030639 to EMC). | pt_BR |
Language | eng | pt_BR |
Publisher | Public Library of Science | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Citotoxicidade imunológica | pt_BR |
Subject in Portuguese | Linfócitos T CD8-positivos | pt_BR |
Subject in Portuguese | Interleucina-1beta | pt_BR |
Subject in Portuguese | Leishmania braziliensis | pt_BR |
Subject in Portuguese | Linfócitos T Citotóxicos | pt_BR |
Subject in Portuguese | Reação em Cadeia da Polimerase em Tempo Real | pt_BR |
Title | CD8+ T cell cytotoxicity mediates pathology in the skin by inflammasome activation and IL-1β production | pt_BR |
Type | Article | pt_BR |
DOI | 10.1371/journal.ppat.1006196 | |
Abstract | Deregulated CD8+ T cell cytotoxicity plays a central role in enhancing disease severity in several conditions. However, we have little understanding of the mechanisms by which immunopathology develops as a consequence of cytotoxicity. Using murine models of inflammation induced by the protozoan parasite leishmania, and data obtained from patients with cutaneous leishmaniasis, we uncovered a previously unrecognized role for NLRP3 inflammasome activation and IL-1β release as a detrimental consequence of CD8+ T cell-mediated cytotoxicity, ultimately resulting in chronic inflammation. Critically, pharmacological blockade of NLRP3 or IL-1β significantly ameliorated the CD8+ T cell-driven immunopathology in leishmania-infected mice. Confirming the relevance of these findings to human leishmaniasis, blockade of the NLRP3 inflammasome in skin biopsies from leishmania-infected patients prevented IL-1β release. Thus, these studies link CD8+ T cell cytotoxicity with inflammasome activation and reveal novel avenues of treatment for cutaneous leishmaniasis, as well as other of diseases where CD8+ T cell-mediated cytotoxicity induces pathology. | pt_BR |
Affilliation | University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA | pt_BR |
Affilliation | Fundação Oswaldo Cruz. 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 |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Complexo Hospitalar Prof. Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Instituto Nacional de Ciências e Tecnologia. Doenças Tropicais. 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. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Complexo Hospitalar Prof. Edgard Santos. Serviço de Imunologia. Salvador, BA, Brasil / Instituto Nacional de Ciências e Tecnologia. Doenças Tropicais. Salvador, BA, Brasil | pt_BR |
Affilliation | University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA | pt_BR |
Subject | Immunologic cytotoxicity | pt_BR |
Subject | CD8-Positive T-Lymphocytes | pt_BR |
Subject | Interleukin-1beta | pt_BR |
Subject | Leishmania braziliensis | pt_BR |
Subject | T-Lymphocytes Cytotoxic | pt_BR |
Subject | Real-Time Polymerase Chain Reaction | pt_BR |