TY - JOUR
T1 - Salmonella Typhimurium Impedes Innate Immunity with a Mast-Cell-Suppressing Protein Tyrosine Phosphatase, SptP
AU - Choi, Hae Woong
AU - Brooking-Dixon, Rhea
AU - Neupane, Subham
AU - Lee, Chul Jin
AU - Miao, Edward A.
AU - Staats, Herman F.
AU - Abraham, Soman N.
N1 - Funding Information:
We thank J. Galán and A. Aballay for Salmonella strains, S. Dowdy for plasmids, D. Metcalfe for LAD2 cells, and A. Roers for Cma1-cre mice. We thank M. Kuehn, L. Hale, and M. Gunn for discussions. C. Shelburne provided technical advice. W. Ang and S. Bowen provided critical manuscript review. This work was funded by National Institutes of Health grants U01-AI082107, R01-AI096305, and R56-DK095198 and a block grant from Duke-NUS, Singapore.
PY - 2013/12/12
Y1 - 2013/12/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84890175289&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2013.11.009
DO - 10.1016/j.immuni.2013.11.009
M3 - Article
AN - SCOPUS:84890175289
SN - 1074-7613
VL - 39
SP - 1108
EP - 1120
JO - Immunity
JF - Immunity
IS - 6
ER -
