DOI: 10.1126/science.1123933. Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response

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

10.1126/science.1123933

Crossref journal-article

American Association for the Advancement of Science (AAAS)

Science (221)

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.

Bibliography

Liu, P. T., Stenger, S., Li, H., Wenzel, L., Tan, B. H., Krutzik, S. R., Ochoa, M. T., Schauber, J., Wu, K., Meinken, C., Kamen, D. L., Wagner, M., Bals, R., Steinmeyer, A., ZuÌgel, U., Gallo, R. L., Eisenberg, D., Hewison, M., Hollis, B. W., â¦ Modlin, R. L. (2006). Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response. Science, 311(5768), 1770â1773.

Authors 22

Philip T. Liu (first)
Steffen Stenger (additional)
Huiying Li (additional)
Linda Wenzel (additional)
Belinda H. Tan (additional)
Stephan R. Krutzik (additional)
Maria Teresa Ochoa (additional)
Jürgen Schauber (additional)
Kent Wu (additional)
Christoph Meinken (additional)
Diane L. Kamen (additional)
Manfred Wagner (additional)
Robert Bals (additional)
Andreas Steinmeyer (additional)
Ulrich Zügel (additional)
Richard L. Gallo (additional)
David Eisenberg (additional)
Martin Hewison (additional)
Bruce W. Hollis (additional)
John S. Adams (additional)
Barry R. Bloom (additional)
Robert L. Modlin (additional)

References 20 Referenced 3,053

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Materials and methods are available as supporting material on Science Online.
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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.

Dates

Type	When
Created	19 years, 6 months ago (Feb. 23, 2006, 8:49 p.m.)
Deposited	1 year, 7 months ago (Jan. 9, 2024, 10:20 p.m.)
Indexed	29 minutes ago (Aug. 29, 2025, 8:03 p.m.)
Issued	19 years, 5 months ago (March 24, 2006)
Published	19 years, 5 months ago (March 24, 2006)
Published Print	19 years, 5 months ago (March 24, 2006)

Funders 0

None

BibTeX

@article{Liu_2006, title={Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response}, volume={311}, ISSN={1095-9203}, url={http://dx.doi.org/10.1126/science.1123933}, DOI={10.1126/science.1123933}, number={5768}, journal={Science}, publisher={American Association for the Advancement of Science (AAAS)}, author={Liu, Philip T. and Stenger, Steffen and Li, Huiying and Wenzel, Linda and Tan, Belinda H. and Krutzik, Stephan R. and Ochoa, Maria Teresa and Schauber, Jürgen and Wu, Kent and Meinken, Christoph and Kamen, Diane L. and Wagner, Manfred and Bals, Robert and Steinmeyer, Andreas and Zügel, Ulrich and Gallo, Richard L. and Eisenberg, David and Hewison, Martin and Hollis, Bruce W. and Adams, John S. and Bloom, Barry R. and Modlin, Robert L.}, year={2006}, month=mar, pages={1770–1773} }

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  "abstract": "<jats:p>\n            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\u2013hydroxylase genes, leading to induction of the antimicrobial peptide cathelicidin and killing of intracellular\n            <jats:italic>Mycobacterium tuberculosis</jats:italic>\n            . 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\u2013mediated innate immunity and suggest that differences in ability of human populations to produce vitamin D may contribute to susceptibility to microbial infection.\n          </jats:p>",
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