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https://www.arca.fiocruz.br/handle/icict/25494
CD8+ T CELL CYTOTOXICITY MEDIATES PATHOLOGY IN THE SKIN BY INFLAMMASOME ACTIVATION AND IL-1β PRODUCTION
Linfócitos T CD8-positivos
Interleucina-1beta
Leishmania braziliensis
Linfócitos T Citotóxicos
Reação em Cadeia da Polimerase em Tempo Real
CD8-Positive T-Lymphocytes
Interleukin-1beta
Leishmania braziliensis
T-Lymphocytes Cytotoxic
Real-Time Polymerase Chain Reaction
Author
Affilliation
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA
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
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA
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
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA
Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA
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
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA
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
University of Pennsylvania. School of Veterinary Medicine. Department of Pathobiology. Philadelphia, Pennsylvania, USA
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.
Keywords in Portuguese
Citotoxicidade imunológicaLinfócitos T CD8-positivos
Interleucina-1beta
Leishmania braziliensis
Linfócitos T Citotóxicos
Reação em Cadeia da Polimerase em Tempo Real
Keywords
Immunologic cytotoxicityCD8-Positive T-Lymphocytes
Interleukin-1beta
Leishmania braziliensis
T-Lymphocytes Cytotoxic
Real-Time Polymerase Chain Reaction
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