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-alpha) and IL-6 production by murine bone-marrow derived macrophages. Production of TNF-alpha 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-alpha and inducible nitric oxide synthase (iNOS) in the liver. Introduction of the cloned viaB region into S. Typhimurium reduced TNF-alpha and iNOS expression to levels observed after infection with a S. Typhimurium msbB mutant. In contrast, no differences in TNF-alpha 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.
Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Ave., Davis, CA, USA.
R Paul
RP
Wilson
Manuela
M
Raffatellu
Daniela
D
Chessa
Sebastian E
SE
Winter
Cagla
C
Tükel
Andreas J
AJ
Bäumler
D000818:Animals; D016667:Bacterial Capsules / Q000276:immunology / Q000502:physiology* / Q000648:ultrastructure; D002460:Cell Line; D005260:Female; D015850:Interleukin-6 / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016253:Microscopy, Immunoelectron; D019001:Nitric Oxide Synthase / Q000378:metabolism; D012485:Salmonella typhi / Q000254:growth & development* / Q000276:immunology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D019001:Nitric Oxide Synthase