沙门氏菌SopB抑制转录后调节的细胞因子释放，以减少早期组织炎症并延缓疾病进展
Salmonella SopB suppresses post-transcriptionally regulated cytokine release to reduce early tissue inflammation and delay disease progression.
摘要(中文译文)
鼠伤寒沙门菌（Salmonella enterica subsp. enterica serovar Typhimurium，S. Typhimurium）通过将效应分子转运至宿主细胞胞质来操纵细胞过程。利用近期建立的新生鼠S. Typhimurium感染模型，我们提供了关于沙门菌外蛋白B（SopB）如何抑制早期黏膜组织炎症并延长宿主存活的功能性见解。机制上，SopB阻止解整合素和金属蛋白酶17（ADAM17）的活化、质膜转位以及肠上皮细胞膜结合型TNFα的释放，并通过mTOR调控的分泌性自噬减少上皮IL-18的分泌。这消除了早期上皮转录反应，减少了免疫细胞募集和程序性细胞死亡介导的黏膜屏障破坏，从而延缓疾病进展。SopB的免疫抑制作用不依赖于其C端编码的磷脂酰肌醇磷酸酶和磷酸转移酶活性，但需要完整的N端结构域。此外，该作用仅限于以沙门菌致病岛（SPI）1型3型分泌系统（T3SS）依赖性肠上皮细胞侵袭驱动的黏膜转位为特征的新生鼠模型。因此，我们在此证明SopB以不依赖肌醇磷酸酶的方式抑制上皮细胞因子释放的早期转录后调控，可能促进病原体传播。
Abstract
Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) manipulates cellular processes through the translocation of effector molecules into the host cell cytosol. Using a recently established neonatal S. Typhimurium infection model, we provide functional insights into how Salmonella outer protein B (SopB) suppresses early mucosal tissue inflammation and prolongs host survival. Mechanistically, SopB prevents a disintegrin and metalloprotease 17 (ADAM17) activation, plasma membrane translocation and the release of membrane-bound TNFα from enterocytes and reduces epithelial secretion of IL-18 via mTOR-controlled secretory autophagy. This abolishes the early epithelial transcriptional response and reduces immune cell recruitment and programmed cell death-mediated mucosal barrier disruption delaying disease progression. The immunosuppressive effect of SopB is independent of the C-terminally encoded phosphatidylinositol phosphatase and phosphotransferase activity but requires an intact N-terminal domain. Also, it is restricted to the neonatal mouse model characterised by Salmonella pathogenicity island (SPI)1 type 3 secretion system (T3SS)-dependent enterocyte invasion-driven mucosal translocation. Thus, here we demonstrate that SopB suppresses the early, post-transcriptional regulation of epithelial cytokine release in an inositol phosphatase-independent manner likely promoting pathogen transmission.
如何引用
AMA
Nour Diab, Chiun Huei Yong, Eva-Lena Stange, Marlène S Birk, Matthias A Schmitz, Stefan Düsterhöft, et al. Salmonella SopB suppresses post-transcriptionally regulated cytokine release to reduce early tissue inflammation and delay disease progression.. Nature communications. 2026; doi:10.1038/s41467-026-74942-9.
APA
Nour Diab, Chiun Huei Yong, Eva-Lena Stange, Marlène S Birk, Matthias A Schmitz, Stefan Düsterhöft, et al (2026). Salmonella SopB suppresses post-transcriptionally regulated cytokine release to reduce early tissue inflammation and delay disease progression.. Nature communications. https://doi.org/10.1038/s41467-026-74942-9
GB/T 7714
Nour Diab, Chiun Huei Yong, Eva-Lena Stange, Marlène S Birk, Matthias A Schmitz, Stefan Düsterhöft, et al. Salmonella SopB suppresses post-transcriptionally regulated cytokine release to reduce early tissue inflammation and delay disease progression.[J]. Nature communications, 2026 doi:10.1038/s41467-026-74942-9.
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