Salmonella Typhimurium Impedes Innate Immunity with a Mast-Cell-Suppressing Protein Tyrosine Phosphatase, SptP

The virulence of Salmonella is linked to its invasive capacity and suppression of adaptive immunity. This does not explain, however, the rapid dissemination of the pathogen after it breaches the gut. In our study, S. Typhimurium suppressed degranulation of local mast cells (MCs), resulting in limited neutrophil recruitment and restricting outflow of vascular contents into infection sites, thus facilitating bacterial spread. MC suppression was mediated by secreted effector protein (SptP), which shares structural homology with Yersinia YopH. SptP functioned by dephosphorylating the vesicle fusion protein N-ethylmalemide-sensitive factor and by blocking phosphorylation of Syk. Without SptP, orally challenged S. Typhimurium failed to suppress MC degranulation and exhibited limited colonization of the mesenteric lymph nodes. Administration of SptP to sites of E. coli infection markedly enhanced its virulence. Thus, SptP-mediated inactivation of local MCs is a powerful mechanism utilized by S. Typhimurium to impede early innate immunity. •Salmonella Typhimurium specifically suppresses mast cell degranulation•Mast cell suppression reduces neutrophil influx early in Salmonella infection•SptP inhibits mast cell degranulation by dephosphorylating Syk and NSF•Compared to WT Salmonella, the SptP mutant is cleared early in infection