Publication: Disruptions in endocytic traffic contribute to the activation of the NLRP3 inflammasome
Authors
Martín Sánchez, María Rosario Fátima ; Lee, Bali ; Hoyle, Christopher ; Wellens, Rose ; Green, Jack P. ; Williams, Daniel M. ; Matchett, Billie J. ; Seoane, Paula I. ; Bennett, Hayley ; Adamson, Antony ; López Castejón, Gloria ; Lowe, Martin ; Brough, David
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Publisher
American Association for the Advancement of Science
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DOI
https://doi.org/10.1126/scisignal.abm7134
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info:eu-repo/semantics/article
Description
Abstract
Inflammation driven by the NLRP3 inflammasome is coordinated through multiple signaling pathways and is regulated by sub-cellular organelles. Here, we tested the hypothesis that NLRP3 senses disrupted endosome trafficking to trigger inflammasome formation and inflammatory cytokine secretion. NLRP3-activating stimuli disrupted endosome trafficking and triggered localization of NLRP3 to vesicles positive for endolysosomal markers and for the inositol lipid PI4P. Chemical disruption of endosome trafficking sensitized macrophages to the NLRP3 activator imiquimod, driving enhanced inflammasome activation and cytokine secretion. Together, these data suggest that NLRP3 can sense disruptions in the trafficking of endosomal cargoes, which may explain in part the spatial activation of the NLRP3 inflammasome. These data highlight mechanisms that could be exploited in the therapeutic targeting of NLRP3.
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Citation
Science Signaling, 2023, Vol 16, Issue 773
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