A VgrG2b fragment cleaved by caspase-11/4 promotes <i>Pseudomonas aeruginosa</i> infection through suppressing the NLRP3 inflammasome.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 39998486.
- Also identified by DOI 10.7554/eLife.99939 and PMC identifier 11856931.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The T6SS of <i>Pseudomonas aeruginosa</i> plays an essential role in the establishment of chronic infections. Inflammasome-mediated inflammatory cytokines are crucial for host defense against bacterial infections. We found that <i>P. aeruginosa</i> infection activates the non-canonical inflammasome in macrophages, yet it inhibits the downstream activation of the NLRP3 inflammasome. The VgrG2b of <i>P. aeruginosa</i> is recognized and cleaved by caspase-11, generating a free C-terminal fragment. The VgrG2b C-terminus can bind to NLRP3, inhibiting the activation of the NLRP3 inflammasome by rejecting NEK7 binding to NLRP3. Administration of a specific peptide that inhibits caspase-11 cleavage of VgrG2b significantly improves mouse survival during infection. Our discovery elucidates a mechanism by which <i>P. aeruginosa</i> inhibits host immune response, providing a new approach for the future clinical treatment of <i>P. aeruginosa</i> infections.
Medical subject headings
- Inflammasomes
- Pseudomonas aeruginosa
- NLR Family, Pyrin Domain-Containing 3 Protein
- Pseudomonas Infections
- Caspases, Initiator
- Caspases
- Bacterial Proteins