Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response
Abstract
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.
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All volunteers in the study were categorized by self-identification or visual determination as African Americans or Caucasians (non-Hispanic, White). There were 19 African Americans and 14 Caucasians studied in Fig. 4, D and E. Although the studies were performed using samples from African Americans, we believe that the implications are likely to be relevant for all individuals of African descent and possibly of Asian decent. Future studies will be directed towards comparing responses according to measured skin pigmentation.
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We would like to thank G. Cheng at UCLA for his helpful discussion and O. Sorensen for the cathelicidin antibody. This work was supported by NIH grants AI47868, AI22553, HD043921, AR50626, AI48176, AI052453, AR45676, and RR00425; and also by the Deutsche Forschungsgemeinschaft (SFB 643 and GRK 592); Deutsche Akademie der Naturforscher Leopoldina; and U.S. Department of Veterans Affairs Merit Award.
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Science
Volume 311 | Issue 5768
24 March 2006
24 March 2006
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American Association for the Advancement of Science.
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Received: 16 December 2005
Accepted: 8 February 2006
Published in print: 24 March 2006
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