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

• Published in: Mucosal immunology Vol. 8; no. 3; pp. 618 - 626
• Main Authors: Chen, J, Waddell, A, Lin, Y-D, Cantorna, M T
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.05.2015; Nature Publishing Group US; Elsevier Limited
• Subjects: 631/250/2504/2506; 631/250/347; 631/80/86/388; 692/4020/1503/2745; Allergology; Animals; Anti-Bacterial Agents - adverse effects; Antibodies; Biomedical and Life Sciences; Biomedicine; Bone Marrow Transplantation; Citrobacter rodentium - immunology; Colony Count, Microbial; Disease Susceptibility; Dysbiosis - chemically induced; Dysbiosis - genetics; Dysbiosis - immunology; Dysbiosis - microbiology; Enterobacteriaceae Infections - genetics; Enterobacteriaceae Infections - immunology; Enterobacteriaceae Infections - microbiology; Enterobacteriaceae Infections - pathology; Fecal Microbiota Transplantation; Gastroenterology; Gene Expression; Germ-Free Life - immunology; Immunology; Interleukin-22; Interleukins - biosynthesis; Interleukins - immunology; Lymphocytes - drug effects; Lymphocytes - immunology; Lymphocytes - microbiology; Mice; Mice, Knockout; Microbiota - drug effects; Microbiota - immunology; Receptors, Calcitriol - deficiency; Receptors, Calcitriol - genetics; Receptors, Calcitriol - immunology
• ISSN: 1933-0219; 1935-3456; 1935-3456
• DOI: 10.1038/mi.2014.94

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 interleukin-22 (IL-22)-producing innate lymphoid cells (ILCs) and more antibacterial peptides than WT mice. The increased ILCs in the VDR KO mice was a cell-autonomous effect of VDR deficiency on ILC frequencies. Bone marrow (BM) transplantation from VDR KO mice into WT resulted in higher ILCs 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 germ-free mice resulted in colonization resistance. Once colonization resistance was 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.