Endocrine Abstracts (2010) 21 S5.2

Anti-bacterial action of vitamin D

Martin Hewison


University of California Los Angeles, Los Angeles, California, USA.


Immunomodulatory properties of vitamin D have been recognized for more than 25 years. However, until recently it was unclear whether these actions of contributed to normal immune function. Two new developments have helped to clarify this. Firstly, our perspective on what constitutes normal vitamin D status has changed considerably, with the introduction of the term ‘vitamin D insufficiency’ to describe individuals with inadequate (but not rachitic) serum levels of 25-hydroxyvitamin D (25OHD), the main circulating form of vitamin D. This has led to the conclusion that millions of people worldwide have impaired 25OHD status. Secondly, a series of studies by our group and others have shown that macrophage antibacterial innate immune responses are associated with enhanced conversion of 25OHD to active 1,25-dihydroxyvitamin D (1,25(OH)2D), and elevated expression of the vitamin D receptor (VDR). This intracrine response to vitamin D provides a flexible system for handling pathogens such as Mycobacterium tuberculosis: local synthesis of 1,25(OH)2D promotes synthesis of antimicrobial proteins and enhances key autophagy events required for killing of pathogens. In addition, intracrine metabolism of vitamin D promotes feedback regulation of Toll-like receptor signaling and facilitates communication with the adaptive immune system. These macrophage actions of vitamin D are characterized by localized synthesis of 1,25(OH)2D via the enzyme 1α-hydroxylase (CYP27B1), a reaction which is primarily dependent on the availability of substrate for CYP27B1, namely 25OHD. Thus, innate immune responses to vitamin D will be strongly influenced by the vitamin D status of individuals, and may be compromised in those with vitamin D insufficiency. The implications of this new perspective on the interaction between vitamin D and the immune system will be discussed with particular reference to the mechanisms involved in regulating vitamin D metabolism and the impact on human health.

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