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

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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, Wu, Kent, Meinken, Christoph, Kamen, Diane L., Wagner, Manfred, Bals, Robert, Steinmeyer, Andreas, Zügel, Ulrich, Gallo, Richard L., Eisenberg, David, Hewison, Martin, Hollis, Bruce W., Adams, John S., Bloom, Barry R., Modlin, Robert L.·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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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: Liu, Philip T.
Stenger, Steffen
Li, Huiying
Wenzel, Linda
Tan, Belinda H.
Kamen, Diane L.
Wagner, Manfred
Bals, Robert
Steinmeyer, Andreas
Gallo, Richard L.
Eisenberg, David
Hewison, Martin
Hollis, Bruce W.
Adams, John S.
Bloom, Barry R.
Modlin, Robert L.
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 › Endocrinology, Diabetes and Metabolism › 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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Toll-Like Receptor Triggering of a Vitamin D-Mediated Human Antimicrobial Response

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