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Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response

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.

Published on 10-30-2009
Authors: Philip T. Liu,1,2* Steffen Stenger,4* Huiying Li,3 Linda Wenzel,4 Belinda H. Tan,1,2 Stephan R. Krutzik,2 Maria Teresa Ochoa,2 Jurgen Schauber,5 Kent Wu,1 Christoph Meinken,4 Diane L. Kamen,6 Manfred Wagner,7 Robert Bals,8 Andreas Steinmeyer,9 Ulrich Zugel,10 Richard L. Gallo,5 David Eisenberg,3 Martin Hewison,11 Bruce W. Hollis,12 John S. Adams,11 Barry R. Bloom,13 Robert L. Modlin1,2
Source: Science 24 March 2006: Vol. 311. no. 5768, pp. 1770 - 1773