Departamento de Biomedicina Molecular, Centro de Investigación y Estudios Avanzados del Instituto Politecnico Nacional, Mexico City CP 07360, México.
J Immunol. 2013 Feb 1;190(3):1201-9. doi: 10.4049/jimmunol.1200415. Epub 2013 Jan 2.
Salmonella infects and survives within B cells, but the mechanism used by the bacterium to promote its survival in these cells is unknown. In macrophages, flagellin secreted by Salmonella activates the Nod-like receptor (NLR) family CARD domain containing protein 4 (NLRC4) inflammasome, leading to the production of IL-1β and pyroptosis of infected cells. In this study, we demonstrated that the NLRC4 inflammasome is functional in B cells; however, in Salmonella-infected B cells, IL-1β secretion is prevented through the downregulation of NLRC4 expression. A functional Salmonella pathogenicity island 1 type III secretion system appears to be required for this process. Furthermore, infection induces Yap phosphorylation and promotes the interaction of Yap with Hck, thus preventing the transcriptional activation of NLRC4. The ability of Salmonella to inhibit IL-1β production also prevents B cell death; thus, B cells represent an ideal niche in which Salmonella resides, thereby promoting its persistence and dissemination.
沙门氏菌在 B 细胞中感染和存活，但细菌用于促进其在这些细胞中存活的机制尚不清楚。在巨噬细胞中，沙门氏菌分泌的鞭毛蛋白激活 Nod 样受体（NLR）家族 CARD 结构域包含蛋白 4（NLRC4）炎性小体，导致 IL-1β 的产生和感染细胞的细胞焦亡。在这项研究中，我们证明 NLRC4 炎性小体在 B 细胞中是有功能的；然而，在沙门氏菌感染的 B 细胞中，通过下调 NLRC4 的表达来阻止 IL-1β 的分泌。一个功能性的沙门氏菌致病性岛 1 型 III 型分泌系统似乎是这个过程所必需的。此外，感染诱导 yap 磷酸化，并促进 yap 与 Hck 的相互作用，从而阻止 NLRC4 的转录激活。沙门氏菌抑制 IL-1β 产生的能力也阻止了 B 细胞的死亡；因此，B 细胞代表了沙门氏菌驻留的理想生态位，从而促进其持续存在和传播。
