Caspase-1 cleavage of the TLR adaptor TRIF inhibits autophagy and β-interferon production during Pseudomonas aeruginosa infection
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 vi...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Cell Press
2014
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| _version_ | 1797071714114338816 |
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| author | Jabir, M Ritchie, N Li, D Bayes, H Tourlomousis, P Puleston, D Lupton, A Hopkins, L Simon, A Bryant, C Evans, T |
| author_facet | Jabir, M Ritchie, N Li, D Bayes, H Tourlomousis, P Puleston, D Lupton, A Hopkins, L Simon, A Bryant, C Evans, T |
| author_sort | Jabir, M |
| collection | OXFORD |
| 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. |
| first_indexed | 2024-03-06T22:57:18Z |
| format | Journal article |
| id | oxford-uuid:60e01d62-1a03-4506-9ce0-76b8562808ab |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:57:18Z |
| publishDate | 2014 |
| publisher | Cell Press |
| record_format | dspace |
| spelling | oxford-uuid:60e01d62-1a03-4506-9ce0-76b8562808ab2022-03-26T17:55:58ZCaspase-1 cleavage of the TLR adaptor TRIF inhibits autophagy and β-interferon production during Pseudomonas aeruginosa infectionJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:60e01d62-1a03-4506-9ce0-76b8562808abEnglishSymplectic Elements at OxfordCell Press2014Jabir, MRitchie, NLi, DBayes, HTourlomousis, PPuleston, DLupton, AHopkins, LSimon, ABryant, CEvans, TBacterial 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. |
| spellingShingle | Jabir, M Ritchie, N Li, D Bayes, H Tourlomousis, P Puleston, D Lupton, A Hopkins, L Simon, A Bryant, C Evans, T Caspase-1 cleavage of the TLR adaptor TRIF inhibits autophagy and β-interferon production during Pseudomonas aeruginosa infection |
| title | Caspase-1 cleavage of the TLR adaptor TRIF inhibits autophagy and β-interferon production during Pseudomonas aeruginosa infection |
| title_full | Caspase-1 cleavage of the TLR adaptor TRIF inhibits autophagy and β-interferon production during Pseudomonas aeruginosa infection |
| title_fullStr | Caspase-1 cleavage of the TLR adaptor TRIF inhibits autophagy and β-interferon production during Pseudomonas aeruginosa infection |
| title_full_unstemmed | Caspase-1 cleavage of the TLR adaptor TRIF inhibits autophagy and β-interferon production during Pseudomonas aeruginosa infection |
| title_short | Caspase-1 cleavage of the TLR adaptor TRIF inhibits autophagy and β-interferon production during Pseudomonas aeruginosa infection |
| title_sort | caspase 1 cleavage of the tlr adaptor trif inhibits autophagy and β interferon production during pseudomonas aeruginosa infection |
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