ABSTRACT
It has become increasingly evident that vitamin D has a functional role in innate immunity and inammation. First, vitamin D-induced antimicrobial activity against pathogens is a key component of the monocyte/macrophage response in infectious disease (Liu et al. 2006; Yuk et al. 2009; Gombart 2009; Jo 2010). Second, it is now recognized that vitamin D insufciency/deciency, dened by serum 25D levels, is a clinical problem of global proportions (Oliveri et al. 2004; Rosen 2011; O’Sullivan et al. 2008; Holick 2007; Hollis et al. 2007; Adams and Hewison 2008) and potentially compromises the intracrine metabolism of precursor 25-hydroxyvitamin D3 (25D; Hewison 2010b) to sufcient levels of active 1,25-dihydroxyvitamin D3 (1,25D) in monocytes/macrophages (Adams and Hewison 2008). Consequently, the intracellular or local levels of 1,25D achieved during an immune response are suboptimal and, therefore, not sufcient to activate the necessary downstream immune effector functions. Third, investigations into the vitamin D receptor (VDR) have revealed exaggerated inammatory responses through defects in VDR signaling, suggesting a potential link between decreased circulating vitamin D levels and VDR signaling with chronic inammatory diseases (Sun et al. 2006; Szeto et al. 2007; Zehnder et al. 2008; Proal et al. 2009; Wu and Sun 2011; Liu et al. 2011).
