Dysbiosis caused by vitamin D receptor deficiency confers colonization resistance to Citrobacter rodentium through modulation of innate lymphoid cells.

Abstract

Vitamin D receptor (VDR) knockout (KO) mice had fewer Citrobacter rodentium in the feces than wild-type (WT) mice and the kinetics of clearance was faster in VDR KO than WT mice. VDR KO mice had more IL-22 producing innate lymphoid cells (ILC), and more anti-bacterial peptides than WT mice. The increased ILC in the VDR KO mice was a cell autonomous effect of VDR deficiency on ILC frequencies. BM transplantation from VDR KO mice into WT resulted in higher ILC and colonization resistance of the WT mice. Disruption of the gut microbiota using antibiotics in VDR KO mice reversed colonization resistance to C. rodentium infection. Confirming the role of the microbiota in the colonization resistance of VDR KO mice, transfer of the VDR KO microbiota to WT GF mice, resulted in colonization resistance. Once colonization resistance is overcome, VDR KO mice had increased susceptibility to C. rodentium. VDR expression is a regulator of ILC frequencies, IL-22, dysbiosis and C. rodentium susceptibility.