Activation of Autophagy by Inflammatory Signals Limits IL-1β Production by Targeting Ubiquitinated Inflammasomes for Destruction
By C. Shi, K. Shenderov, N. Huang, J. Kabat, M. Abu-Asab, Katherine A. Fitzgerald, A. Sher, J. Kehrl. Nature Immunology, 2012
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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.
Subfields: Epidemiology, Immunology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/0d822a4b97320bae800594461e0f77cb64b71f52
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Citations in the corpus
- Regulation of inflammasome activation (2015, background): “Activation of the AIM2 or NLRP3 inflammasomes results in polyubiquitination of ASC, which induces the recruitment of the autophagic marker, p62, to target the inflammasome for autophagic degradation (198).”
- Autophagy and lysosomal dysfunction as emerging mechanisms of nanomaterial toxicity (2012, background): “Nanomaterialinduced autophagy blockade may also be a mechanism of nanomaterial-associated inflammation, as there is evidence that autophagy plays an important role in negatively regulating the NLRP3 inflammasome [110].”
- PAMPs and DAMPs: Signal 0s that Spur Autophagy and Immunity (2012, background): “Various inflammasome stimuli trigger autophagy in macrophages by activating nucleotide exchange (the replacement of GDP by GTP) on RalB (190).”
- Gasdermins: Effectors of pyroptosis (2017, background): “How can a cell release IL-1β/IL-18 through a gasdermin pore without lysing soon after? Theoretically, a cell with few gasdermin pores could shut off the inflammasome[31], remove the pores through exocytic patching mechanisms[22–24], and survive.”