Dexamethasone modulates Salmonella enterica serovar Typhimurium infection in vivo independently of the glucocorticoid-inducible protein annexin-A1

FEMS Immunol Med Microbiol. 2008 Dec;54(3):339-48. doi: 10.1111/j.1574-695X.2008.00485.x.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A1 / genetics
  • Annexin A1 / metabolism*
  • Dexamethasone / pharmacology*
  • Glucocorticoids / pharmacology*
  • Liver / drug effects
  • Liver / microbiology
  • Liver / pathology
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Salmonella Infections, Animal / immunology*
  • Salmonella Infections, Animal / microbiology
  • Salmonella Infections, Animal / pathology
  • Salmonella typhimurium / drug effects*
  • Salmonella typhimurium / growth & development
  • Salmonella typhimurium / pathogenicity*
  • Spleen / drug effects
  • Spleen / microbiology
  • Spleen / pathology

Substances

  • Annexin A1
  • Glucocorticoids
  • Dexamethasone