Klebsiella pneumoniae hijacks the Toll-IL-1R protein SARM1 in a type I IFN-dependent manner to antagonize host immunity.
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2022Access:
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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-Download Item:
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.
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http://people.tcd.ie/cartymihttp://people.tcd.ie/agbowie
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Author: Carty, Michael; Bowie, Andrew
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Cell Reports;40;
6;
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AIM2 inflammasome; CP: Immunology; CP: Microbiology; Klebsiella pneumoniae; SARM1; type I IFNDOI:
http://dx.doi.org/10.1016/j.celrep.2022.111167Metadata
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