title: Dexamethasone modulates Salmonella enterica serovar Typhimurium infection in vivo independently of the glucocorticoid-inducible protein annexin-A1.
abstract: Salmonella enterica serovar Typhimurium (S. Typhimurium) infection causes an inflammatory response through activation of Toll-like receptor 4 by lipopolysaccharide. Dexamethasone, a glucocorticoid analogue, suppresses inflammatory responses by many mechanisms including inhibition of the lipopolysaccharide-induced production of proinflammatory mediators. There is little information on the effect of glucocorticoids on murine salmonellosis. In this study, we treated susceptible BALB/c mice by subcutaneous implantation of slow-release dexamethasone pellets before infection with S. Typhimurium. Dexamethasone promotes bacterial growth early in infection and induces a dose-dependent increase in bacterial growth within mouse livers and spleens. The bacterial load in organs from infected placebo-treated mice was lower than that in dexamethasone-treated mice. Glucocorticoids inhibit lipopolysaccharide-induced inflammation partially through the steroid-inducible protein annexin-A1 (ANXA1). Infection of wild-type and ANXA1 knock-out mice with S. Typhimurium led to similar organ bacterial loads. ANXA1 also did not affect the bacterial load in organs from infected dexamethasone-treated mice. This suggests that glucocorticoids, independently of ANXA1, accelerate S. Typhimurium growth in vivo in susceptible BALB/c mice.
authors.affiliation: Department of Veterinary Medicine, The University of Cambridge, Cambridge, UK.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Smyth
authors.forename: Sabine
authors.initials: S
authors.lastname: Tötemeyer
authors.forename: Sean
authors.initials: S
authors.lastname: Haugland
authors.forename: Chrissie
authors.initials: C
authors.lastname: Willers
authors.forename: Sarah
authors.initials: S
authors.lastname: Peters
authors.forename: Duncan
authors.initials: D
authors.lastname: Maskell
authors.forename: Clare
authors.initials: C
authors.lastname: Bryant
mesh_terms: D000818:Animals; D017305:Annexin A1 / Q000235:genetics / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D012486:Salmonella typhimurium / Q000187:drug effects* / Q000254:growth & development / Q000472:pathogenicity*; D013154:Spleen / Q000187:drug effects / Q000382:microbiology / Q000473:pathology
chemical_list: D017305:Annexin A1; D005938:Glucocorticoids; D003907:Dexamethasone