Vitamin D3 contribution to systemic and local control of Salmonella Typhimurium infection in an in vivo mouse model

Introduction Vitamin D serves as a critical modulator of innate and adaptive immune responses. Its active metabolite, 1,25-dihydroxyvitamin D3 (1,25(OH) 2 D 3 ), exhibits potent antimicrobial activity in both humans and mice, positioning it as a promising adjunctive or alternative therapeutic for infectious diseases through immune modulation and clearance of pathogens. Among these, Salmonella enterica serovar Typhimurium, a leading cause of foodborne zoonotic infections, presents significant global public health burdens. Methods Employing an in vivo murine model, we recapitulated the systemic and gastrointestinal features of S. Typhimurium-induced acute salmonellosis, which elicits a vigorous pro-inflammatory cytokine response that exacerbates pathogenesis while facilitating bacterial persistence. In this context, we evaluated the therapeutic potential of 1,25(OH) 2 D 3 in an S. Typhimurium colitis model, examining its effects on infection severity, systemic immunity, and enteric immune dynamics. At three days post-infection, assessments encompassed bacterial colonization, flow cytometric analysis of peripheral blood leukocytes, and histopathological evaluation of tissues. Results Our findings demonstrate that 1,25(OH) 2 D 3 administration confers multifaceted protective effects, including reduced bacterial burden, attenuated histopathological inflammation, modulated immune cell profiles, and prolonged survival, thereby promoting infection resolution over progression. Discussion These results underscore the immunomodulatory efficacy of vitamin D in combating S. Typhimurium infection and warrant further exploration for clinical translation.