NLRP3 activation in response to disrupted endocytic trafficCitation formats

  • External authors:
  • Bali Lee
  • Rose Wellens
  • Fatima Martín-Sánchez
  • Daniel Williams
  • Paula Seoane Denicola
  • Martin Lowe
  • David Brough

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NLRP3 activation in response to disrupted endocytic traffic. / Lee, Bali; Hoyle, Christopher; Green, Jack et al.

In: bioRxiv, 16.09.2021.

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Lee B, Hoyle C, Green J, Wellens R, Martín-Sánchez F, Williams D et al. NLRP3 activation in response to disrupted endocytic traffic. bioRxiv. 2021 Sep 16.

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Bibtex

@article{5ba2e05bbf654aa68bc9f70e6ed6ddd1,
title = "NLRP3 activation in response to disrupted endocytic traffic",
abstract = "Inflammation driven by the NLRP3 inflammasome is coordinated through multiple signaling pathways and with a poorly defined regulation 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 endosome markers and the inositol lipid PtdIns4P. 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 is capable of sensing disruptions in the trafficking of endosomal cargoes, and that this may explain in part the spatial activation of the NLRP3 inflammasome complex. These data highlight new mechanisms amenable for the therapeutic targeting of NLRP3.",
author = "Bali Lee and Christopher Hoyle and Jack Green and Rose Wellens and Fatima Mart{\'i}n-S{\'a}nchez and Daniel Williams and {Seoane Denicola}, Paula and Hayley Bennett and Antony Adamson and Gloria Lopez-Castejon and Martin Lowe and David Brough",
year = "2021",
month = sep,
day = "16",
language = "English",
journal = "bioRxiv",
issn = "2692-8205",
publisher = "Cold Spring Harbor Laboratory Press",

}

RIS

TY - JOUR

T1 - NLRP3 activation in response to disrupted endocytic traffic

AU - Lee, Bali

AU - Hoyle, Christopher

AU - Green, Jack

AU - Wellens, Rose

AU - Martín-Sánchez, Fatima

AU - Williams, Daniel

AU - Seoane Denicola, Paula

AU - Bennett, Hayley

AU - Adamson, Antony

AU - Lopez-Castejon, Gloria

AU - Lowe, Martin

AU - Brough, David

PY - 2021/9/16

Y1 - 2021/9/16

N2 - Inflammation driven by the NLRP3 inflammasome is coordinated through multiple signaling pathways and with a poorly defined regulation 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 endosome markers and the inositol lipid PtdIns4P. 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 is capable of sensing disruptions in the trafficking of endosomal cargoes, and that this may explain in part the spatial activation of the NLRP3 inflammasome complex. These data highlight new mechanisms amenable for the therapeutic targeting of NLRP3.

AB - Inflammation driven by the NLRP3 inflammasome is coordinated through multiple signaling pathways and with a poorly defined regulation 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 endosome markers and the inositol lipid PtdIns4P. 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 is capable of sensing disruptions in the trafficking of endosomal cargoes, and that this may explain in part the spatial activation of the NLRP3 inflammasome complex. These data highlight new mechanisms amenable for the therapeutic targeting of NLRP3.

M3 - Article

JO - bioRxiv

JF - bioRxiv

SN - 2692-8205

ER -