title: Salmonella typhimurium impedes innate immunity with a mast-cell-suppressing protein tyrosine phosphatase, SptP.
abstract: 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.
authors: Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
authors: Hae Woong
authors: HW
authors: Choi
authors: Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
authors: Rhea
authors: R
authors: Brooking-Dixon
authors: Undergraduate Program in Biology, Duke University Medical Center, Durham, NC 27710, USA.
authors: Subham
authors: S
authors: Neupane
authors: Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA.
authors: Chul-Jin
authors: CJ
authors: Lee
authors: Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors: Edward A
authors: EA
authors: Miao
authors: Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA; Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA; Duke Human Vaccine Institute, Duke University Medical Center, Durham, NC 27710, USA.
authors: Herman F
authors: HF
authors: Staats
authors: Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA; Department of Immunology, Duke University Medical Center, Durham, NC 27710, USA; Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA; Program in Emerging Infectious Diseases, Duke - National University of Singapore Graduate Medical School, Singapore 169857, Singapore. Electronic address: soman.abraham@duke.edu.
authors: Soman N
authors: SN
authors: Abraham
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D015550:Cell Degranulation; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D008407:Mast Cells / Q000276:immunology / Q000382:microbiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009504:Neutrophils / Q000276:immunology; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D012480:Salmonella Infections / Q000276:immunology* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D015010:Yersinia pestis / Q000201:enzymology
chemical_list: D001426:Bacterial Proteins; D017027:Protein Tyrosine Phosphatases; C439890:sptP protein, Salmonella typhimurium