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Vitamin D Is Required for IFN- -Mediated Antimicrobial Activity of Human Macrophages
Fabri, M.,Stenger, S.,Shin, D.-M.,Yuk, J.-M.,Liu, P. T.,Realegeno, S.,Lee, H.-M.,Krutzik, S. R.,Schenk, M.,Sieling, P. A.,Teles, R.,Montoya, D.,Iyer, S. S.,Bruns, H.,Lewinsohn, D. M.,Hollis, B. W.,Hew American Association for the Advancement of Scienc 2011 Science translational medicine Vol.3 No.104
<P>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.</P>