PT  - JOURNAL ARTICLE
AU  - Claudia Feriotti
AU  - Joana Sa-Pessoa
AU  - Ricardo Calderón-González
AU  - Lili Gu
AU  - Brenda Morris
AU  - Ryoichi Sugisawa
AU  - Jose L. Insua
AU  - Michael Carty
AU  - Amy Dumigan
AU  - Rebecca J. Ingram
AU  - Adrien Kisenpfening
AU  - Andrew G. Bowie
AU  - José A. Bengoechea
TI  - <em>Klebsiella pneumoniae</em> hijacks the Toll-IL-1R protein SARM1 in a type I IFN-dependent manner to antagonize host immunity
AID  - 10.1101/2021.09.29.462388
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.09.29.462388
4099  - http://biorxiv.org/content/early/2021/09/29/2021.09.29.462388.short
4100  - http://biorxiv.org/content/early/2021/09/29/2021.09.29.462388.full
AB  - Many bacterial pathogens antagonize host defence 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 hijacks the evolutionary conserved innate immune protein SARM1 to control cell intrinsic immunity. Klebsiella exploits 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 IL10 by fine-tuning the p38-type I IFN axis. SARM1 inhibits the activation of Klebsiella-induced absent in melanoma 2 inflammasome to limit IL1β production, suppressing further inflammation. Klebsiella exploits type I IFNs to induce SARM1 in a capsule and LPS O-polysaccharide-dependent manner via TLR4-TRAM-TRIF-IRF3-IFNAR1 pathway. Absence of SARM1 reduces the intracellular survival of K. pneumonaie in macrophages whereas sarm1 deficient mice control the infection. Altogether, our results illustrate a hitherto unknown anti-immunology strategy deployed by a human pathogen.Competing Interest StatementThe authors have declared no competing interest.