Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response
Philip T. LiuDivision of Dermatology, Department of Medicine, David Geffen School of Medicine; University of California at Los Angeles, Los Angeles, CA 90095, USASteffen StengerInstitut für Klinische Mikrobiologie, Immunologie, und Hygiene, Universität Erlangen, D-91054 Erlangen, GermanyHuiying LiDivision of Dermatology, University of California at San Diego, and Veterans Affairs San Diego Healthcare Center, San Diego, CA 92161, USALinda WenzelDivision of Dermatology, Department of Medicine, David Geffen School of Medicine; University of California at Los Angeles, Los Angeles, CA 90095, USABelinda H. TanDepartment of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USAStephan R. KrutzikDepartment of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USAMarîa Teresa OchoaDepartment of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USAJürgen SchauberInstitut für Klinische Mikrobiologie, Immunologie, und Hygiene, Universität Erlangen, D-91054 Erlangen, GermanyKent WuDepartment of Microbiology, Immunology, and Molecular Genetics; 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. KamenDivision of Dermatology, Department of Medicine, David Geffen School of Medicine; University of California at Los Angeles, Los Angeles, CA 90095, USAManfred WagnerDepartment of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USARobert BalsDivision of Dermatology, Department of Medicine, David Geffen School of Medicine; University of California at Los Angeles, Los Angeles, CA 90095, USAAndreas SteinmeyerDivision of Dermatology, Department of Medicine, David Geffen School of Medicine; University of California at Los Angeles, Los Angeles, CA 90095, USAUlrich ZügelDepartment of Microbiology, Immunology, and Molecular Genetics; 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 HewisonDivision of Dermatology, Department of Medicine, David Geffen School of Medicine; 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 Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USABarry R. BloomDivision of Dermatology, University of California at San Diego, and Veterans Affairs San Diego Healthcare Center, San Diego, CA 92161, 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
Annotatsiya
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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