Vitamin D promotes anti-microbial activity of macrophages via Complement Receptor Immunoglobulin

Abstract

Abstract Vitamin D deficiency remains of major global concern, affecting up to half of the population at some stage of life. Although the use of vitamin D to treat infections has been studied over several decades, the mechanisms involved still remain to be elucidated. There has been a major focus on the effects of vitamin D on innate immunity and macrophages, one of the few cell types that can synthesize active vitamin D. Here, we examined whether vitamin D exerts its anti-microbial effects through Complement Receptor Immunoglobulin (CRIg), a phagocytosis-promoting receptor unique to macrophages. Using a series of in vitro culture methods of human macrophages, we show that CRIg expression by macrophages is increased at the mRNA and protein level by the active derivative 1,25-dihydroxyvitamin D (1,25D), while having no effect on the expression of the classical complement receptors, CR3 (CD11b) and CR4 (CD11c). This upregulation of CRIg was associated with an enhanced anti-microbial capability by the cell against the pathogens Staphylococcus aureus and Candida albicans. Furthermore, using the synthetic triacylated lipopeptide Pam3CSK4, we show that macrophages require activation to convert vitamin D to the active 1,25D, which then in turn acts in an autocrine manner to upregulate expression of CRIg. These findings suggest that a major innate defense mechanism against both bacterial and fungal pathogens controlled by vitamin D is through the regulation of CRIg expression in macrophages.