Klebsiella pneumoniae hijacks the Toll-IL-1R protein SARM1 in a type I IFN-dependent manner to antagonize host immunity

被引：23

作者：

Feriotti, Claudia ^{[1
]}

Sa-Pessoa, Joana ^{[1
]}

Calderon-Gonzalez, Ricardo ^{[1
]}

Gu, Lili ^{[2
]}

Morris, Brenda ^{[1
]}

Sugisawa, Ryoichi ^{[2
]}

Insua, Jose L. ^{[1
]}

Carty, Michael ^{[2
]}

Dumigan, Amy ^{[1
]}

Ingram, Rebecca J. ^{[1
]}

Kissenpfening, Adrien ^{[1
]}

Bowie, Andrew G. ^{[2
]}

Bengoechea, Jose A. ^{[1
,2
]}

机构：

[1] Queens Univ Belfast, Wellcome Wolfson Inst Expt Med, Sch Med Dent & Biomed Sci, 97 Lisburn Rd, Belfast, Antrim, North Ireland

[2] Trinity Coll Dublin, Trin Biomed Sci Inst, Sch Biochem & Immunol, Dublin 2, Ireland

来源：

CELL REPORTS | 2022年 / 40卷 / 06期

基金：

英国生物技术与生命科学研究理事会; 爱尔兰科学基金会;

关键词：

DOMAIN-CONTAINING ADAPTERS; 2 INFLAMMASOME ACTIVATION; NF-KAPPA-B; AIM2; INFLAMMASOME; NLRP3; CAPSULAR POLYSACCHARIDE; NEUTROPHIL RECRUITMENT; IL-10; PRODUCTION; CUTTING EDGE; MURINE MODEL;

D O I：

10.1016/j.celrep.2022.111167

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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-1 beta 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.

引用

页数：28

共 94 条

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