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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Caspase-1 cleavage of the TLR adaptor TRIF inhibits autophagy and β-interferon production during pseudomonas aeruginosa infection
Cell Host and Microbe, Volume 15, No. 2, Year 2014
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Description
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. © 2014 Elsevier Inc.
Authors & Co-Authors
Jabir, Majid Sakhi
Unknown Affiliation
Ritchie, Neil D.
Unknown Affiliation
Li, Dong
Unknown Affiliation
Bayes, Hannah Kelly
Unknown Affiliation
Tourlomousis, Panagiotis
Unknown Affiliation
Puleston, Daniel
Unknown Affiliation
Lupton, Alison
Unknown Affiliation
Hopkins, Lee
Unknown Affiliation
Simon, Anna Katharina
Unknown Affiliation
Bryant, Clare
Unknown Affiliation
Evans, Thomas J.
Unknown Affiliation
Statistics
Citations: 83
Authors: 11
Affiliations: 6
Identifiers
Doi:
10.1016/j.chom.2014.01.010
ISSN:
19313128
e-ISSN:
19346069