Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages.

Fabri, Mario; Stenger, Steffen; Shin, Dong-Min; Yuk, Jae-Min; Liu, Philip T; Realegeno, Susan; Lee, Hye-Mi; Krutzik, Stephan R; Schenk, Mirjam; Sieling, Peter A; Teles, Rosane; Montoya, Dennis; Iyer, Shankar S; Bruns, Heiko; Lewinsohn, David M; Hollis, Bruce W; Hewison, Martin; Adams, John S; Steinmeyer, Andreas; Zügel, Ulrich; ... (2011). Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages. Science translational medicine, 3(104), 104ra102. American Association for the Advancement of Science 10.1126/scitranslmed.3003045

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Control of tuberculosis worldwide depends on our understanding of human immune mechanisms, which combat the infection. Acquired T cell responses are critical for host defense against microbial pathogens, yet the mechanisms by which they act in humans remain unclear. We report that T cells, by the release of interferon-γ (IFN-γ), induce autophagy, phagosomal maturation, the production of antimicrobial peptides such as cathelicidin, and antimicrobial activity against Mycobacterium tuberculosis in human macrophages via a vitamin D-dependent pathway. IFN-γ induced the antimicrobial pathway in human macrophages cultured in vitamin D-sufficient sera, but not in sera from African-Americans that have lower amounts of vitamin D and who are more susceptible to tuberculosis. In vitro supplementation of vitamin D-deficient serum with 25-hydroxyvitamin D3 restored IFN-γ-induced antimicrobial peptide expression, autophagy, phagosome-lysosome fusion, and antimicrobial activity. These results suggest a mechanism in which vitamin D is required for acquired immunity to overcome the ability of intracellular pathogens to evade macrophage-mediated antimicrobial responses. The present findings underscore the importance of adequate amounts of vitamin D in all human populations for sustaining both innate and acquired immunity against infection.

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