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Cited by 3,924Immune Response and InflammationVitamin D Research StudiesTuberculosis Research and Epidemiology

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

Liu, Philip T., Stenger, Steffen, Li, Huiying, Wenzel, Linda, Tan, Belinda H., Krutzik, Stephan R., Ochoa, Maria Teresa, Schauber, Jürgen +14 more·2006·Science
DOI 10.1126/science.1123933
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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.

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Crossref · 10.1126/science.1123933

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  • Activation of Toll-like receptor 1 and TLR2 by tuberculosis enhances 1α-hydroxylase expression, production of antimicrobial peptide cathelicidin, and induction of tolerogenic dendritic cells and T cells.

    “Activation of Toll-like receptor 1 (TLR1) and TLR2 by tuberculosis enhances 1α-hydroxylase expression, the enzyme mediates the synthesis of 1,25(OH)2D3, production of antimicrobial peptide cathelicidin [87], and induction of tolerogenic DCs and T cells [60,84].”

    From Molecular Mechanisms of UV-Induced Apoptosis and Its Effects on Skin Residential Cells: The Implication in UV-Based Phototherapy (2013) · cites this paper as [87]

  • Expression of the vitamin D receptor and vitamin D converting hydroxylases, mainly CYP27b1, is induced after TLR2 activation of human monocytes/macrophages.

    “The expression of this latter receptor as well as the vitamin D converting hydroxylases, mainly vitamin D-1 hydroxylase CYP27b1, is induced after TLR2 activation of human monocytes/macrophages (82).”

    From Macrophage defense mechanisms against intracellular bacteria (2015) · cites this paper as [82]

  • Induction of cathelicidin in human keratinocytes and monocytes in skin wounds or upon infection is enhanced by 1,25 vitamin D3.

    “Induction of cathelicidin in human keratinocytes and monocytes in skin wounds or upon infection is enhanced by 1,25 vitamin D3.42,43”

    From The Innate Immune System in Acute and Chronic Wounds (2016) · cites this paper as [42]

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Authors
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., Zügel, U., Gallo, R. L., Eisenberg, D., Hewison, M., Hollis, B. W., Adams, J. S., Bloom, B. R., & Modlin, R. L.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Department of Microbiology, Immunology, and Molecular Genetics; University of California at Los Angeles, Los Angeles, CA 90095, USA.
Corresponding author
  • Liu, Philip T.
  • Stenger, Steffen
  • Modlin, Robert L.
ORCID
Venue
Science
Publisher
American Association for the Advancement of Science (AAAS)
Published
2006-03-24
Volume
311
Issue
5768
Pages
1770-1773
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
DOI
10.1126/science.1123933
OpenAlex
W2124580054
Cited by
3,924
References
24
Citations by year
2026: 80 · 2025: 126 · 2024: 101 · 2023: 197 · 2022: 185 · 2021: 222 · 2020: 213 · 2019: 171 · 2018: 181 · 2017: 215 · 2016: 217 · 2015: 239 · 2014: 252 · 2013: 221 · 2012: 266
FWCI
67.99
Type
journal article
Language
en
Open access
closed
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • University of Birmingham Research Portal (University of Birmingham) (submittedVersion)
Funders
  • National Institute of Allergy and Infectious Diseases (AI48176, AI-22553, R21AI048176, K22AI085025, AI 47868, AI 052453)
  • National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR 45676, R01AR045676, AR50626, R01AR050626)
  • National Center for Research Resources (RR00425, M01RR000425)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (HD043921, R01HD043921)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Vitamin D Research Studies
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
Keywords
Toll-like receptors, vitamin D, vitamin D receptor, 25-hydroxyvitamin D, cathelicidin, antimicrobial peptides, Mycobacterium tuberculosis, human macrophages, innate immunity, tuberculosis susceptibility, African American population, intracellular bacterial killing
MeSH terms
Black or African American, Calcitriol, Dendritic Cells, Disease Susceptibility, Humans, Immunity, Innate, Macrophages, Monocytes, Mycobacterium tuberculosis, RNA, Messenger, Steroid Hydroxylases, Tuberculosis, 25-Hydroxyvitamin D3 1-alpha-Hydroxylase, Colony Count, Microbial, Up-Regulation, Receptors, Calcitriol, Oligonucleotide Array Sequence Analysis, Antimicrobial Cationic Peptides, Toll-Like Receptors, Cathelicidins, Vitamin D3 24-Hydroxylase

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