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

DOI Web Site 48 Citations
  • Philip T. Liu
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Steffen Stenger
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Huiying Li
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Linda Wenzel
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Belinda H. Tan
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Stephan R. Krutzik
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Maria Teresa Ochoa
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Jürgen Schauber
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Kent Wu
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Christoph Meinken
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Diane L. Kamen
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Manfred Wagner
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Robert Bals
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Andreas Steinmeyer
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Ulrich Zügel
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Richard L. Gallo
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • David Eisenberg
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Martin Hewison
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Bruce W. Hollis
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • John S. Adams
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Barry R. Bloom
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
  • Robert L. Modlin
    Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.

Abstract

<jats:p> 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 <jats:italic>Mycobacterium tuberculosis</jats:italic> . 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. </jats:p>

Journal

  • Science

    Science 311 (5768), 1770-1773, 2006-03-24

    American Association for the Advancement of Science (AAAS)

Citations (48)*help

See more

Keywords

Details 詳細情報について

Report a problem

Back to top