Abstract
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 language | English |
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Pages (from-to) | 104ra102 |
Journal | Science Translational Medicine |
Volume | 3 |
Issue number | 104 |
DOIs | |
Publication status | Published - 12 Oct 2011 |
Keywords
- Anti-Infective Agents
- Antimicrobial Cationic Peptides
- Autophagy
- Calcifediol
- Humans
- Interferon-gamma
- Lymphocyte Activation
- Macrophages
- Models, Biological
- Monocytes
- Mycobacterium tuberculosis
- Tuberculosis
- Vitamin D