Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response
Philip T. LiuDepartment 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, USASteffen StengerDepartment 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, USAHuiying LiDepartment 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, USALinda WenzelDepartment 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, USABelinda H. TanDepartment 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, USAStephan R. KrutzikDepartment 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, USAMarîa Teresa OchoaDepartment 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, USAJürgen SchauberDepartment 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, USAKent WuDepartment 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, USAChristoph MeinkenDepartment 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, USADiane L. KamenDepartment 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, USAManfred WagnerDepartment 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, USARobert BalsDepartment 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, USAAndreas SteinmeyerDepartment 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, USAUlrich ZügelDepartment 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, USARichard L. GalloDepartment 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, USADavid EisenbergDepartment 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, USAMartin HewisonDepartment 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, USABruce W. HollisDepartment 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, USAJohn S. AdamsDepartment 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, USABarry R. BloomDepartment 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, USARobert L. ModlinDepartment 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
2006en
ABI
Аннотация
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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