Active vitamin D3 attenuates the severity of Salmonella colitis in mice by orchestrating innate immunity

Introduction: Salmonella spp. pose major public health problems worldwide. A better understanding of the pathogenesis of these foodborne pathogens is a prerequisite for the design of improved intervention strategies that could reduce the use of antimicrobial agents and drug-resistant Salmonellosis. Accumulating evidence indicates that vitamin D is involved in regulating innate immunity, and may, therefore, play a key role in human responses to infection. Studies have suggested 1,25-dihydroxyvitamin D3 (1,25D3), the active form of vitamin D, effectively ameliorates colitis. These findings have broad implications for the use of vitamin D compounds in colitis. This study investigated the effect of active vitamin D3 on the severity of Salmonella colitis. Methods: A Salmonella colitis model was established with 6–8-week-old male C57BL/6 mice: Streptomycin-pretreated C57BL/6 mice were infected orally with Salmonella enterica serova Typhimurium wild-type strain SL1344 for 48 h. The mice were randomly assigned to control, model, and 1,25(OH)₂D₃-treated groups. After the experiment, the mice were sacrificed, and intestinal, spleen, and liver tissue samples were removed to analyze bacterial colonization, western blot for protein levels, and real-time-polymer chain reaction for messenger RNA (mRNA) expression. Results: We observed that 1,25D3 reduced the severity of Salmonella colitis in C57BL/6 mice by reducing cecal mIL-1beta, mIL-6, mTNF-alpha, and mIL-8 mRNA expressions, bacterial colonization (CFU/mg tissue) in the liver and spleen, but increased the human β-defensin-2 mRNA and autophagy protein expression, compared to those of the SL1344 infection only. Conclusions: Our results document that active vitamin D3 reduced Salmonella colitis by decreasing inflammation, and bacterial translocation via induction of killing and autophagic clearance of pathogenic organisms.