Open AccessThe Vi‐capsule prevents Toll‐like receptor 4 recognition of Salmonella
Author(s) -
Wilson R. Paul,
Raffatellu Manuela,
Chessa Daniela,
Winter Sebastian E.,
Tükel Çagla,
Bäumler Andreas J.
Publication year - 2008
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/j.1462-5822.2007.01090.x
Subject(s) - biology , tlr4 , lipopolysaccharide , tumor necrosis factor alpha , microbiology and biotechnology , salmonella enterica , toll like receptor , salmonella , receptor , immunology , innate immune system , bacteria , biochemistry , genetics
Summary The viaB locus enables Salmonella enterica serotype Typhi to reduce Toll‐like receptor (TLR) dependent cytokine production in tissue culture models. This DNA region contains genes involved in the regulation ( tviA ), biosynthesis ( tviBCDE ) and export ( vexABCDE ) of the Vi capsule. Expression of the Vi capsule in S. Typhimurium, but not expression of the TviA regulatory protein, reduced tumour necrosis factor‐alpha (TNF‐α) and IL‐6 production by murine bone‐marrow derived macrophages. Production of TNF‐α and IL‐6 was dependent on expression of TLR4 as stimulation of macrophages from TLR4 −/− mice with S. Typhimurium did not result in expression of these cytokines. Intraperitoneal infection of mice with S. Typhimurium induced expression of TNF‐α and inducible nitric oxide synthase (iNOS) in the liver. Introduction of the cloned viaB region into S. Typhimurium reduced TNF‐α and iNOS expression to levels observed after infection with a S. Typhimurium msbB mutant. In contrast, no differences in TNF‐α expression between the S. Typhimurium wild type and strains expressing the Vi‐capsule or carrying a mutation in msbB were observed after infection of TLR4 −/− mice. We conclude that the Vi capsule prevents both in vitro and in vivo recognition of S. Typhimurium lipopolysaccharide by TLR4.