Qian Yan, Liu Qiannv, Cheng Xiangyun, Wang Chunlei, Kong Chun, Li Mengqian, Ren Chao, Jiang Dong, Wang Shuo, Xia Pengyan
Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.
NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China.
Elife. 2025 Feb 25;13:RP99939. doi: 10.7554/eLife.99939.
The T6SS of plays an essential role in the establishment of chronic infections. Inflammasome-mediated inflammatory cytokines are crucial for host defense against bacterial infections. We found that infection activates the non-canonical inflammasome in macrophages, yet it inhibits the downstream activation of the NLRP3 inflammasome. The VgrG2b of is recognized and cleaved by caspase-11, generating a free C-terminal fragment. The VgrG2b C-terminus can bind to NLRP3, inhibiting the activation of the NLRP3 inflammasome by rejecting NEK7 binding to NLRP3. Administration of a specific peptide that inhibits caspase-11 cleavage of VgrG2b significantly improves mouse survival during infection. Our discovery elucidates a mechanism by which inhibits host immune response, providing a new approach for the future clinical treatment of infections.
[细菌名称]的VI型分泌系统（T6SS）在慢性感染的建立中起着至关重要的作用。炎性小体介导的炎性细胞因子对于宿主抵御细菌感染至关重要。我们发现，[细菌名称]感染可激活巨噬细胞中的非经典炎性小体，但它会抑制NLRP3炎性小体的下游激活。[细菌名称]的VgrG2b被caspase-11识别并切割，产生一个游离的C末端片段。VgrG2b的C末端可与NLRP3结合，通过阻止NEK7与NLRP3结合来抑制NLRP3炎性小体的激活。给予一种抑制caspase-11对VgrG2b切割的特异性肽可显著提高感染期间小鼠的存活率。我们的发现阐明了[细菌名称]抑制宿主免疫反应的机制，为未来[细菌名称]感染的临床治疗提供了新方法。
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