title: Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction.
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.
authors.affiliation: B cell Molecular Immunology Section, Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, US National Institutes of Health, Bethesda, Maryland, USA. cshi@niaid.nih.gov
authors.forename: Chong-Shan
authors.initials: CS
authors.lastname: Shi
authors.forename: Kevin
authors.initials: K
authors.lastname: Shenderov
authors.forename: Ning-Na
authors.initials: NN
authors.lastname: Huang
authors.forename: Juraj
authors.initials: J
authors.lastname: Kabat
authors.forename: Mones
authors.initials: M
authors.lastname: Abu-Asab
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Fitzgerald
authors.forename: Alan
authors.initials: A
authors.lastname: Sher
authors.forename: John H
authors.initials: JH
authors.lastname: Kehrl
mesh_terms: D000818:Animals; D001343:Autophagy; D002352:Carrier Proteins / Q000276:immunology; D002460:Cell Line; D004268:DNA-Binding Proteins; D006801:Humans; D058847:Inflammasomes / Q000276:immunology* / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000096:biosynthesis* / Q000276:immunology; D051379:Mice; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009687:Nuclear Proteins / Q000276:immunology; D015398:Signal Transduction; D054875:Ubiquitination; D020725:ral GTP-Binding Proteins / Q000276:immunology
chemical_list: C540422:Aim2 protein, mouse; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D009687:Nuclear Proteins; C535173:RalB protein, mouse; D020725:ral GTP-Binding Proteins