dc.contributor.author | Carty, Michael | |
dc.contributor.author | Bowie, Andrew | |
dc.date.accessioned | 2024-05-20T15:09:30Z | |
dc.date.available | 2024-05-20T15:09:30Z | |
dc.date.issued | 2022 | |
dc.date.submitted | 2022 | en |
dc.identifier.citation | Feriotti C, Sá-Pessoa J, Calderón-González R, Gu L, Morris B, Sugisawa R, Insua JL, Carty M, Dumigan A, Ingram RJ, Kissenpfening A, Bowie AG, Bengoechea JA. Klebsiella pneumoniae hijacks the Toll-IL-1R protein SARM1 in a type I IFN-dependent manner to antagonize host immunity, Cell Reports, 40, 6, 2022, 111167- | en |
dc.identifier.other | Y | |
dc.description | PUBLISHED | en |
dc.description.abstract | Many bacterial pathogens antagonize host defense responses by translocating effector proteins into cells. It remains an open question how those pathogens not encoding effectors counteract anti-bacterial immunity. Here, we show that Klebsiella pneumoniae exploits the evolutionary conserved innate protein SARM1 to regulate negatively MyD88- and TRIF-governed inflammation, and the activation of the MAP kinases ERK and JNK. SARM1 is required for Klebsiella induction of interleukin-10 (IL-10) by fine-tuning the p38-type I interferon (IFN) axis. SARM1 inhibits the activation of Klebsiella-induced absent in melanoma 2 inflammasome to limit IL-1β production, suppressing further inflammation. Klebsiella exploits type I IFNs to induce SARM1 in a capsule and lipopolysaccharide O-polysaccharide-dependent manner via the TLR4-TRAM-TRIF-IRF3-IFNAR1 pathway. Absence of SARM1 reduces the intracellular survival of K. pneumoniae in macrophages, whereas sarm1-deficient mice control the infection. Altogether, our results illustrate an anti-immunology strategy deployed by a human pathogen. SARM1 inhibition will show a beneficial effect to treat Klebsiella infections. | en |
dc.format.extent | 111167 | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | Cell Reports; | |
dc.relation.ispartofseries | 40; | |
dc.relation.ispartofseries | 6; | |
dc.rights | Y | en |
dc.subject | AIM2 inflammasome; CP: Immunology; CP: Microbiology; Klebsiella pneumoniae; SARM1; type I IFN | en |
dc.title | Klebsiella pneumoniae hijacks the Toll-IL-1R protein SARM1 in a type I IFN-dependent manner to antagonize host immunity. | en |
dc.type | Journal Article | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/cartymi | |
dc.identifier.peoplefinderurl | http://people.tcd.ie/agbowie | |
dc.identifier.rssinternalid | 238104 | |
dc.identifier.doi | http://dx.doi.org/10.1016/j.celrep.2022.111167 | |
dc.rights.ecaccessrights | openAccess | |
dc.identifier.rssuri | https://www.sciencedirect.com/science/article/pii/S2211124722009809?via%3Dihub | |
dc.identifier.orcid_id | 0000-0003-1588-7479 | |
dc.status.accessible | N | en |
dc.identifier.uri | http://hdl.handle.net/2262/108440 | |