Salmonella Downregulates Nod-like Receptor Family CARD Domain Containing Protein 4 Expression To Promote Its Survival in B Cells by Preventing Inflammasome Activation and Cell Death

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-1 beta 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-1 beta 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-1 beta production also prevents B cell death; thus, B cells represent an ideal niche in which Salmonella resides, thereby promoting its persistence and dissemination. The Journal of Immunology, 2013, 190: 1201-1209.