Klebsiella pneumoniae hijacks the Toll-IL-1R protein SARM1 in a type I IFN-dependent manner to antagonize host immunity.
Klebsiella pneumoniae hijacks the Toll-IL-1R protein SARM1 in a type I IFN-dependent manner to antagonize host immunity.
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DOI：
10.1016/j.celrep.2022.111167
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发表时间：
2022-08-09
期刊：
影响因子：
8.8
通讯作者：
Bengoechea, Jose A.
中科院分区：
文献类型：
--
作者：
Feriotti, Claudia;Sa-Pessoa, Joana;Calderon-Gonzalez, Ricardo;Gu, Lili;Morris, Brenda;Sugisawa, Ryoichi;Insua, Jose L.;Carty, Michael;Dumigan, Amy;Ingram, Rebecca J.;Kissenpfening, Adrien;Bowie, Andrew G.;Bengoechea, Jose A.
许多细菌病原体通过将效应蛋白易位到细胞中来拮抗宿主防御反应。这些不编码效应子的病原体如何对抗抗细菌免疫仍然是一个悬而未决的问题。在这里，我们表明，肺炎克雷伯氏菌利用进化保守的先天蛋白SARM 1负调节MyD 88和TRIF控制的炎症，和MAP激酶ERK和JNK的激活。SARM 1是克雷伯氏菌通过微调p38-I型干扰素（IFN）轴诱导白细胞介素-10（IL-10）所必需的。SARM 1抑制克雷伯氏菌诱导的黑色素瘤2炎性小体的激活，以限制IL-1β的产生，抑制进一步的炎症。克雷伯氏菌利用I型IFN以囊膜和脂多糖O-多糖依赖性方式通过TLR 4-TRAM-TRIF-IRF 3-IFNAR 1途径诱导SARM 1。SARM 1的缺失降低了巨噬细胞中肺炎克雷伯菌的细胞内存活，而SARM 1缺陷小鼠控制了感染。总之，我们的研究结果说明了人类病原体部署的抗免疫学策略。SARM 1抑制将显示出治疗克雷伯氏菌感染的有益效果。SARM 1是一种进化上保守的先天免疫蛋白，具有TIR结构域。肺炎克雷伯氏菌诱导SARM 1限制炎症，并诱导IL-10。SARM 1抑制AIM 2炎性小体的作用，限制IL-1β的产生。揭示肺炎克雷伯氏菌如何利用保守的先天免疫蛋白SARM 1来限制炎症并诱导IL-10。SARM 1还抑制肺炎克雷伯菌诱导的AIM 2炎性小体。在体内，SARM 1的缺乏促进了病原体的清除，揭示了克雷伯氏菌利用我们免疫系统的致命弱点。
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. SARM1 is an evolutionary conserved innate immune protein with a TIR domain Klebsiella pneumoniae induces SARM1 to limit inflammation, and to induce IL-10 SARM1 inhibits the action of AIM2 inflammasome to limit IL-1β production In vivo, absence of SARM1 facilitates the clearance of Klebsiella pneumoniae Feriotti et al. uncover how Klebsiella pneumoniae exploits the conserved innate immune protein SARM1 to limit inflammation and to induce IL-10. SARM1 also inhibits K. pneumoniae-induced AIM2 inflammasome. In vivo, absence of SARM1 facilitates the clearance of the pathogen, revealing an Achilles heel of our immune system exploited by Klebsiella.
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朊病毒样聚合是抗病毒免疫防御和炎症小体激活中信号转导的基础。
影响因子：
64.5
作者：
Cai X;Chen J;Xu H;Liu S;Jiang QX;Halfmann R;Chen ZJ
通讯作者：
Chen ZJ
影响因子：
3.1
作者：
BrougHolub, E;Toews, GB;Standiford, TJ
通讯作者：
Standiford, TJ
影响因子：
3.1
作者：
Bartholomew, Toby L.;Kidd, Timothy J.;Bengoechea, Jose A.
通讯作者：
Bengoechea, Jose A.
影响因子：
8.8
作者：
Bratkowski, Matthew;Xie, Tian;Sambashivan, Shilpa
通讯作者：
Sambashivan, Shilpa
DOI：
10.4049/jimmunol.1200195
发表时间：
2012-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cai S;Batra S;Wakamatsu N;Pacher P;Jeyaseelan S
通讯作者：
Jeyaseelan S