Disruptions in endocytic traffic contribute to the activation of the NLRP3 inflammasome-Reference-Cited by-同舟云学术

Disruptions in endocytic traffic contribute to the activation of the NLRP3 inflammasome

Published:2023-02-21 Issue:773 Volume:16 Page:
ISSN:1945-0877
Container-title:Science Signaling
language:en
Short-container-title:Sci. Signal.

Author:

Lee Bali¹²³^ORCID,Hoyle Christopher¹²³^ORCID,Wellens Rose¹²³^ORCID,Green Jack P.¹²³^ORCID,Martin-Sanchez Fatima³⁴^ORCID,Williams Daniel M.¹⁵^ORCID,Matchett Billie J.¹²³^ORCID,Seoane Paula I.¹²³^ORCID,Bennett Hayley⁶^ORCID,Adamson Antony⁶^ORCID,Lopez-Castejon Gloria³⁴,Lowe Martin⁷^ORCID,Brough David¹²³^ORCID

Affiliation:

1. Division of Neuroscience, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester Academic Health Science Centre, Manchester M13 9PT, UK.

2. Geoffrey Jefferson Brain Research Centre, Manchester Academic Health Science Centre, Northern Care Alliance NHS Group, University of Manchester, Manchester M13 9PT, UK.

3. Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester M13 9PT, UK.

4. Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK.

5. Department of Biomedical Science, Centre for Membrane Interactions and Dynamics, University of Sheffield, Firth Court, Sheffield S10 2TN, UK.

6. Genome Editing Unit, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PT, UK.

7. Division of Molecular and Cellular Function, School of Biological Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre, University of Manchester, Manchester M13 9PT, UK.

Abstract

Inflammation driven by the NLRP3 inflammasome is coordinated through multiple signaling pathways and is regulated by subcellular 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Cell Biology,Molecular Biology,Biochemistry

Link

https://www.science.org/doi/pdf/10.1126/scisignal.abm7134

Reference31 articles.

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