Journal
FRONTIERS IN IMMUNOLOGY
Volume 10, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2019.00001
Keywords
vitamin D; ILC3; IL-22; gastrointestinal infection; Th17
Categories
Funding
- National Institutes of Health [R01AT005378]
- United State Department of Agriculture [2914-38420-21822]
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Citrobacter rodentium is a gastrointestinal infection that requires early IL-22 from group 3 innate lymphoid cells (ILC3) for resistance. The role of vitamin D in the clearance of C. rodentium infection was tested in vitamin D sufficient (D+) and vitamin D deficient (D-) wildtype (WT) and Cyp27B1 (Cyp) KO mice (unable to produce the high affinity vitamin D ligand 1,25(OH)(2)D, 1,25D). Feeding Cyp KO mice D-diets reduced vitamin D levels and prevented synthesis of 1,25D. D-(WT and Cyp KO) mice had fewer ILC3 cells and less IL-22 than D+ mice. D-Cyp KO mice developed a severe infection that resulted in the lethality of the mice by d14 post-infection. T and B cell deficient D-Rag KO mice also developed a severe and lethal infection with C. rodentium compared to D+ Rag KO mice. D-WT mice survived the infection but took significantly longer to clear the C. rodentium infection than D+ WT or D+ Cyp KO mice. Treating infected D-Cyp KO mice with IL-22 protected the mice from lethality. Treating the D-WT mice with 1,25D reconstituted the ILC3 cells in the colon and protected the mice from C. rodentium. IL-22 treatment of D-WT mice eliminated the need for vitamin D to clear the C. rodentium infection. Vitamin D is required for early IL-22 production from ILC3 cells and protection from enteric infection with C. rodentium.
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