Activation of Autophagy by Inflammatory Signals Limits IL-1β Production by Targeting Ubiquitinated Inflammasomes for Destruction
Chong-Shan Shi,Kevin Shenderov,Ning Na Huang,Juraj Kabat,Mones Abu-Asab,Katherine A. Fitzgerald,Alan Sher,John H. Kehrl +7 more
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TLDR
It is shown that the induction of AIM2 or NLRP3 inflammasomes in macrophages triggered activation of the G protein RalB and autophagosome formation, which indicates that autophagy accompaniesinflammasome activation to temper inflammation by eliminating active inflammaomes.Abstract:
Autophagosomes delivers cytoplasmic constituents to lysosomes for degradation, whereas inflammasomes are molecular platforms activated by infection or stress that regulate the activity of caspase-1 and the maturation of interleukin 1β (IL-1β) and IL-18. Here we show that the induction of AIM2 or NLRP3 inflammasomes in macrophages triggered activation of the G protein RalB and autophagosome formation. The induction of autophagy did not depend on the adaptor ASC or capase-1 but was dependent on the presence of the inflammasome sensor. Blocking autophagy potentiated inflammasome activity, whereas stimulating autophagy limited it. Assembled inflammasomes underwent ubiquitination and recruited the autophagic adaptor p62, which assisted their delivery to autophagosomes. Our data indicate that autophagy accompanies inflammasome activation to temper inflammation by eliminating active inflammasomes.read more
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