The dynamic immunomodulatory effects of vitamin D₃ during Mycobacterium infection

Mycobacterium tuberculosis ( Mtb), is a highly infectious airborne bacterium. Previous studies have found vitamin D₃ to be a key factor in the defense against Mtb infection, through its regulation of the production of immune-related cytokines, chemokines and effector molecules. Mycobacterium smegmatis was used in our study as a surrogate of Mtb. We hypothesized that the continuous presence of vitamin D₃, as well as the level of severity of infection would differentially modulate host cell immune response in comparison with control and the vehicle, ethanol. We found that vitamin D₃ conditioning promotes increased bacterial clearance during low-level infection, intracellular containment during high-level infection, and minimizes host cytotoxicity. In the presence of vitamin D₃ host cell production of cytokines and effector molecules was infection-level dependent, most notably IL-12, which increased during high-level infection and decreased during low-level infection, and NO, which had a rate of change positively correlated to IL-12. Our study provides evidence that vitamin D₃ modulation is context-dependent and time-variant, as well as highly correlated to level of infection. This study furthers our mechanistic understanding of the dual role of vitamin D₃ as a regulator of bactericidal molecules and protective agent against host cell damage.