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.

Species-specific regulation of innate immunity by vitamin D signaling

“…The authors noted that the dysbiosis observed in the knockout animals was accompanied by lower levels of tolerogenic dendritic cells in the gut and an increased sensitivity to intestinal inflammation [33]. More recent work by the group showed that the intestines of VDR-null mice were richer in IL-22-producing innate lymphoid cells (ILCs) and were resistant to the murine pathogen Citrobacter rodentium [34]. IL-22 is an innate immune cytokine produced by a subclass of ILCs (ILC3s) that signals through epithelial cells to bolster intestinal innate immunity through enhancing the production of AMPs and components of the mucosal layer [35,36].…”

Vitamin D Deficiency Is Associated With the Severity of Radiation-Induced Proctitis in Cancer Patients

“…Deficiency of vitamin D and VDR signaling results in dysbiosis and impaired host defense against bacterial pathogens (26)(27)(28)(29)(30). Gut microbiota plays a role in the pathogenesis of cancer treatmenteinduced gastrointestinal mucositis.…”

Role of Vitamin D in the Hygiene Hypothesis: The Interplay between Vitamin D, Vitamin D Receptors, Gut Microbiota, and Immune Response

“…For example, a study in pregnant mice showed that maternal supplementation of 25 µg/kg vitamin D prior to an injection of 100 µg/kg of LPS-activated VDR signaling, which inhibited the pro-inflammatory NF-kB p65 pathway and genetic expression of the inflammatory cytokines TNF-α, IL-Iβ, and IL-6 (98). On the other hand, VDRs may contribute to maintenance of intestinal barrier function by preventing increased intestinal permeability, dysbiosis, inflammation, and a lack of immune tolerance in the gut (82).…”