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

Mario Fabri, Steffen Stenger, Dong-Min Shin, Jae-Min Yuk, Philip T Liu, Susan Realegeno, Hye-Mi Lee, Stephan R Krutzik, Mirjam Schenk, Peter A Sieling, Rosane Teles, Dennis Montoya, Shankar S Iyer, Heiko Bruns, David M Lewinsohn, Bruce W Hollis, Martin Hewison, John S Adams, Andreas Steinmeyer, Ulrich ZügelGenhong Cheng, Eun-Kyeong Jo, Barry R Bloom, Robert L Modlin

Research output: Contribution to journalArticlepeer-review

355 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)104ra102
JournalScience Translational Medicine
Issue number104
Publication statusPublished - 12 Oct 2011


  • Anti-Infective Agents
  • Antimicrobial Cationic Peptides
  • Autophagy
  • Calcifediol
  • Humans
  • Interferon-gamma
  • Lymphocyte Activation
  • Macrophages
  • Models, Biological
  • Monocytes
  • Mycobacterium tuberculosis
  • Tuberculosis
  • Vitamin D


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