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

American Association for the Advancement of Science (AAAS) - Tập 311 Số 5768 - Trang 1770-1773 - 2006
Philip T. Liu1,2,3,4,5, Steffen Stenger1,2,3,4,5, Huiying Li1,2,3,4,5, Linda Wenzel1,2,3,4,5, Belinda H. Tan1,2,3,4,5, Stephan R. Krutzik1,2,3,4,5, María Teresa Ochoa1,2,3,4,5, Jürgen Schauber1,2,3,4,5, Kuan‐Hsing Wu1,2,3,4,5, Christoph Meinken1,2,3,4,5, Diane L. Kamen1,2,3,4,5, Manfred Wagner1,2,3,4,5, Robert Bals1,2,3,4,5, Andreas Steinmeyer1,2,3,4,5, Ulrich Zügel1,2,3,4,5, Richard L. Gallo1,2,3,4,5, David Eisenberg1,2,3,4,5, Martin Hewison1,2,3,4,5, Bruce W. Hollis1,2,3,4,5, John S. Adams1,2,3,4,5, Barry R. Bloom1,2,3,4,5, Robert L. Modlin1,2,3,4,5
1Department of Chemistry and Biological Chemistry, Howard Hughes Medical Institute; and Department of Energy Institute of Genomics and Proteomics, University of California at Los Angeles, Los Angeles, CA 90095, USA.
2Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
3Division of Dermatology, Department of Medicine, David Geffen School of Medicine; University of California at Los Angeles, Los Angeles, CA 90095, USA.
4Division of Dermatology, University of California at San Diego, and Veterans Affairs San Diego Healthcare Center, San Diego, CA 92161, USA.
5Institut für Klinische Mikrobiologie, Immunologie, und Hygiene, Universität Erlangen, D-91054 Erlangen, Germany.

Tóm tắt

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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Tài liệu tham khảo

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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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American Association for the Advancement of Science (AAAS)

Tập 311 Số 5768

1770-1773

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