Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages.
Vitamin D is required for IFN-gamma-mediated antimicrobial activity of human macrophages.
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DOI：
10.1126/scitranslmed.3003045
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发表时间：
2011-10-12
影响因子：
17.1
通讯作者：
Modlin RL
中科院分区：
文献类型：
--
作者：
Fabri M;Stenger S;Shin DM;Yuk JM;Liu PT;Realegeno S;Lee HM;Krutzik SR;Schenk M;Sieling PA;Teles R;Montoya D;Iyer SS;Bruns H;Lewinsohn DM;Hollis BW;Hewison M;Adams JS;Steinmeyer A;Zügel U;Cheng G;Jo EK;Bloom BR;Modlin RL
全世界结核病的控制取决于我们对人类免疫机制的理解，这种机制可以对抗感染。获得性T细胞应答对于宿主防御微生物病原体至关重要，但它们在人体中的作用机制仍不清楚。我们报道了T细胞通过释放干扰素-γ（IFN-γ）诱导自噬、吞噬体成熟、抗菌肽（如凯萨林菌素）的产生以及通过维生素D依赖性途径对人巨噬细胞中结核分枝杆菌的抗菌活性。IFN-γ在维生素D充足的血清中培养的人巨噬细胞中诱导了抗菌途径，但在维生素D含量较低且更易患结核病的非洲裔美国人血清中则没有。在体外补充维生素D缺乏的血清与25-羟基维生素D3恢复IFN-γ诱导的抗菌肽的表达，自噬，吞噬体-溶酶体融合，和抗菌活性。这些结果表明，获得性免疫需要维生素D来克服细胞内病原体逃避巨噬细胞介导的抗菌反应的能力。目前的研究结果强调了所有人群中足量维生素D对维持先天和获得性免疫力对抗感染的重要性。
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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DOI：
10.1084/jem.175.4.1111
发表时间：
1992-04-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chan J;Xing Y;Magliozzo RS;Bloom BR
通讯作者：
Bloom BR
DOI：
10.1016/0041-3879(85)90035-2
发表时间：
1985-01-01
期刊：
TUBERCLE
影响因子：
--
作者：
GRANGE, JM;DAVIES, PDO;KARDJITO, T
通讯作者：
KARDJITO, T
影响因子：
4.8
作者：
Gombart, AF;Borregaard, N;Koeffler, HP
通讯作者：
Koeffler, HP
影响因子：
56.9
作者：
Brightbill, HD;Libraty, DH;Modlin, RL
通讯作者：
Modlin, RL
影响因子：
4.8
作者：
Herdick, M;Steinmeyer, A;Carlberg, C
通讯作者：
Carlberg, C