Active vitamin D (1,25-dihydroxyvitamin D3) increases host susceptibility to Citrobacter rodentium by suppressing mucosal Th17 responses

Am J Physiol Gastrointest Liver Physiol. 2012 Dec 15;303(12):G1299-311. doi: 10.1152/ajpgi.00320.2012. Epub 2012 Sep 27.


Vitamin D deficiency affects more that 1 billion people worldwide and is associated with an increased risk of developing a number of inflammatory/autoimmune diseases, including inflammatory bowel disease (IBD). At present, the basis for the impact of vitamin D on IBD and mucosal immune responses is unclear; however, IBD is known to reflect exaggerated immune responses to luminal bacteria, and vitamin D has been shown to play a role in regulating bacteria-host interactions. Therefore, to test the effect of active vitamin D on host responses to enteric bacteria, we gave 1,25(OH)(2)D(3) to mice infected with the bacterial pathogen Citrobacter rodentium, an extracellular microbe that causes acute colitis characterized by a strong Th1/Th17 immune response. 1,25(OH)(2)D(3) treatment of infected mice led to increased pathogen burdens and exaggerated tissue pathology. In association with their increased susceptibility, 1,25(OH)(2)D(3)-treated mice showed substantially reduced numbers of Th17 T cells within their infected colons, whereas only modest differences were noted in Th1 and Treg numbers. In accordance with the impaired Th17 responses, 1,25(OH)(2)D(3)-treated mice showed defects in their production of the antimicrobial peptide REG3γ. Taken together, these studies show that 1,25(OH)(2)D(3) suppresses Th17 T-cell responses in vivo and impairs mucosal host defense against an enteric bacterial pathogen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcitriol / adverse effects*
  • Citrobacter rodentium / drug effects
  • Citrobacter rodentium / immunology*
  • Disease Susceptibility / chemically induced
  • Disease Susceptibility / immunology
  • Disease Susceptibility / pathology
  • Enterobacteriaceae Infections / chemically induced*
  • Enterobacteriaceae Infections / immunology*
  • Enterobacteriaceae Infections / pathology
  • Immunity, Innate / drug effects
  • Immunity, Innate / immunology
  • Immunocompromised Host / drug effects
  • Immunocompromised Host / immunology*
  • Intestinal Mucosa / drug effects
  • Intestinal Mucosa / immunology*
  • Intestinal Mucosa / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Th17 Cells / immunology*


  • Calcitriol