Caspase-1 cleavage of the TLR adaptor TRIF inhibits autophagy and β-interferon production during Pseudomonas aeruginosa infection.

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Item Type:	Article
Title:	Caspase-1 cleavage of the TLR adaptor TRIF inhibits autophagy and β-interferon production during Pseudomonas aeruginosa infection.
Creators Name:	Jabir, M.S., Ritchie, N.D., Li, D., Bayes, H.K., Tourlomousis, P., Puleston, D., Lupton, A., Hopkins, L., Simon, A.K., Bryant, C. and Evans, T.J.
Abstract:	Bacterial infection can trigger autophagy and inflammasome activation, but the effects of inflammasome activation on autophagy are unknown. We examined this in the context of Pseudomonas aeruginosa macrophage infection, which triggers NLRC4 inflammasome activation. P. aeruginosa induced autophagy via TLR4 and its adaptor TRIF. NLRC4 and caspase-1 activation following infection attenuated autophagy. Caspase-1 directly cleaved TRIF to diminish TRIF-mediated signaling, resulting in inhibition of autophagy and in reduced type I interferon production. Expression of a caspase-1 resistant TRIF mutant enhanced autophagy and type I interferon production following infection. Preventing TRIF cleavage by caspase-1 in an in vivo model of P. aeruginosa infection resulted in enhanced bacterial autophagy, attenuated IL-1β production, and increased bacterial clearance. Additionally, TRIF cleavage by caspase-1 diminished NLRP3 inflammasome activation. Thus, caspase-1 mediated TRIF cleavage is a key event in controlling autophagy, type I interferon production, and inflammasome activation with important functional consequences.
Keywords:	Apoptosis Regulatory Proteins, Autophagy, Calcium-Binding Proteins, Caspase 1, Cultured Cells, Hydrolysis, Inbred C57BL Mice, Interferon-beta, Knockout Mice, Macrophages, Pseudomonas Aeruginosa, Toll-Like Receptor 4, Vesicular Transport Adaptor Proteins, Animals, Mice
Source:	Cell Host & Microbe
ISSN:	1931-3128
Publisher:	Elsevier / Cell Press
Volume:	15
Number:	2
Page Range:	214-227
Date:	12 February 2014
Official Publication:	https://doi.org/10.1016/j.chom.2014.01.010
PubMed:	View item in PubMed

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