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CD8+ T cell cytotoxicity mediates pathology in the skin by inflammasome activation and IL-1β production
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CD8+ T cell cytotoxicity mediates pathology in the skin by inflammasome activation and IL-1β production
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Journal Article
CD8+ T cell cytotoxicity mediates pathology in the skin by inflammasome activation and IL-1β production
2017
Overview
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.
Publisher
Public Library of Science,Public Library of Science (PLoS)
Subject
/ CD8-Positive T-Lymphocytes - immunology
/ Cytotoxicity, Immunologic - immunology
/ Humans
/ Interleukin-1beta - biosynthesis
/ Interleukin-1beta - immunology
/ Leishmaniasis, Cutaneous - immunology
/ Leishmaniasis, Cutaneous - metabolism
/ Leishmaniasis, Cutaneous - pathology
/ Medicine and health sciences
/ Mice
/ NLR Family, Pyrin Domain-Containing 3 Protein - immunology
/ Real-Time Polymerase Chain Reaction
