The dynamic immunomodulatory effects of vitamin D₃duringMycobacteriuminfection

Abstract

Mycobacterium tuberculosis ( Mtb), is a highly infectious airborne bacterium. Previous studies have found vitamin D 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 D, 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 D conditioning promotes increased bacterial clearance during low-level infection, intracellular containment during high-level infection, and minimizes host cytotoxicity. In the presence of vitamin D 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 D 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 D as a regulator of bactericidal molecules and protective agent against host cell damage.

Host-Directed Therapy as a Novel Treatment Strategy to Overcome Tuberculosis: Targeting Immune Modulation

“…Several studies have reported the positive association between active TB and low levels of serum vitamin D at diagnosis and during the course of treatment with anti-TB drugs [138,139]. Vitamin D inhibits the proliferation of Mtb inside the macrophages through stimulation of the innate immune responses during the infection [140]. In addition, vitamin D has also an impact on the differentiation of naïve T cells to regulatory T cells, and regulates the function of cytotoxic T cells, indicating a potential role in adaptive immunity during infections [141].…”

Vitamin D and tuberculosis: where next?

“…Disruption of endothelial stability and an enhanced vascular leakage caused by inflammation may enhance disease progression in several inflammatory disorders that are typically associated with low vitamin D status. It has also been suggested that vitamin D‐induced effects are dependent on the multiplicity of Mtb infection (MOI), as 1,25(OH) 2 D restricted bacterial growth by macrophages at low MOIs, whilst it mainly reduced host cytotoxicity at high MOIs .…”

Is there a link between vitamin D status, SARS‐CoV‐2 infection risk and COVID‐19 severity?

“…This action enhances iron efflux from the cells and, thus, limits the iron availability for bacteria 105,106 . Actually, antimicrobial actions of vitamin D are wider than those here reported and include improvement of the gut 107,108 and lung 109 epithelial barrier function, generation of reactive oxygen species, 110 enhancing neutrophils function 111 and phagocytic and autophagocytic (via induction of LC3, beclin 1 and PI3KC3, key effectors of autophagy 112‐116 ) activity of macrophages 112 . Vitamin D‐mediated induction of cathelicidin and defensins also impair viral replication 117,118 and enhancement of autophagy in APC, which is involved in antigen presenting, also helps in clearing up viruses 119,120 .…”