Vitamin D and antibacterial immunity

Vitamin D insufficiency, defined by low levels of circulating 25-hydroxyvitamin D (25(OH)D), is associated with elevated risk of bacterial infections, such as urinary tract infections. It has also been linked to increased risk of inflammatory bowel conditions such as Crohn's disease, which are caused by impaired intestinal innate immunity. In response to pathogen detection and a cytokine network, cells of the innate immune cells generate hormonal vitamin D (calcitriol or 1,25(OH)2D) locally from circulating 25(OH)D. 1,25(OH)2D-mediated protection against bacterial threats is characterized mechanistically by its transcriptional induction of genes encoding several components of innate immune responses: pattern recognition receptors, cytokines, and most notably antimicrobial peptides (AMPs), via stimulation of the vitamin D receptor (VDR). Cathelicidin antimicrobial peptide (CAMP/LL-37), β-defensin 2 (DEFB2/DEFB4/HBD2), and hepcidin (HAMP) are among the antimicrobial proteins regulated by vitamin D. Autophagy represents another important facet of vitamin D–regulated immune signaling, as a block in 1,25(OH)2D-stimulated autophagy results in uncontrolled bacterial replication in macrophages infected with pathogens such as Mycobacterium tuberculosis, the etiological agent of tuberculosis. There is likely more to uncover in this relatively new field of research. Future investigation of 1,25(OH)2D biology in other, critical albeit lesser-studied immune cell populations has the potential to reveal new mechanisms of vitamin D–mediated antibacterial immunity. Furthermore, awareness of the significance of vitamin D in regulating antibacterial immunity may fuel the development of novel vitamin D analogs, which may be used in combination therapies to combat the emerging threat of antibiotic-resistant infections.