The Vi-capsule prevents Toll-like receptor 4 recognition of Salmonella

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.