Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response
Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response
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DOI：
10.1126/science.1123933
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发表时间：
2006-03-24
期刊：
影响因子：
56.9
通讯作者：
Modlin, RL
中科院分区：
文献类型：
--
作者：
Liu, PT;Stenger, S;Modlin, RL
在先天性免疫应答中，Toll样受体（TLR）的激活触发针对细胞内细菌的直接抗微生物活性，其在鼠而非人单核细胞和巨噬细胞中主要由一氧化氮介导。我们在这里报告，TLR激活人类巨噬细胞上调维生素D受体和维生素D-1-羟化酶基因的表达，导致诱导的抗菌肽cathelicidin和杀死细胞内结核分枝杆菌。我们还观察到，已知对结核病易感性增加的非洲裔美国人的血清中25-羟基维生素D含量低，并且在支持cathelicidin信使RNA诱导方面效率低下。这些数据支持TLR和维生素D介导的先天免疫之间的联系，并表明人类群体产生维生素D的能力差异可能有助于对微生物感染的易感性。
In innate immune responses, activation of Toll-like receptors (TLRs) triggers direct antimicrobial activity against intracellular bacteria, which in murine, but not human, monocytes and macrophages is mediated principally by nitric oxide. We report here that TLR activation of human macrophages up-regulated expression of the vitamin D receptor and the vitamin D-1-hydroxylase genes, leading to induction of the antimicrobial peptide cathelicidin and killing of intracellular Mycobacterium tuberculosis. We also observed that sera from African-American individuals, known to have increased susceptibility to tuberculosis, had low 25-hydroxyvitamin D and were inefficient in supporting cathelicidin messenger RNA induction. These data support a link between TLRs and vitamin D-mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection.