Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response

Philip T Liu; Steffen Stenger; Huiying Li; Linda Wenzel; Belinda H Tan; Stephan R Krutzik; Maria Teresa Ochoa; Jürgen Schauber; Kent Wu; Christoph Meinken; Diane L Kamen; Manfred Wagner; Robert Bals; Andreas Steinmeyer; Ulrich Zügel; Richard L Gallo; David Eisenberg; Martin Hewison; Bruce W Hollis; John S Adams; Barry R Bloom; Robert L Modlin

doi:10.1126/science.1123933

Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response

Philip T Liu, Steffen Stenger, Huiying Li, Linda Wenzel, Belinda H Tan, Stephan R Krutzik, Maria Teresa Ochoa, Jürgen Schauber, Kent Wu, Christoph Meinken, Diane L Kamen, Manfred Wagner, Robert Bals, Andreas Steinmeyer, Ulrich Zügel, Richard L Gallo, David Eisenberg, Martin Hewison, Bruce W Hollis, John S AdamsBarry R Bloom, Robert L Modlin

Metabolism and Systems Research

Research output: Contribution to journal › Article › peer-review

2693 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1770-3
Number of pages	4
Journal	Science
Volume	311
Issue number	5768
DOIs	https://doi.org/10.1126/science.1123933
Publication status	Published - 24 Mar 2006

Keywords

25-Hydroxyvitamin D3 1-alpha-Hydroxylase
African Americans
Antimicrobial Cationic Peptides
Calcitriol
Cathelicidins
Colony Count, Microbial
Dendritic Cells
Disease Susceptibility
Humans
Immunity, Innate
Macrophages
Monocytes
Mycobacterium tuberculosis
Oligonucleotide Array Sequence Analysis
RNA, Messenger
Receptors, Calcitriol
Steroid Hydroxylases
Toll-Like Receptors
Tuberculosis
Up-Regulation
Vitamin D3 24-Hydroxylase

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1126/science.1123933

Cite this

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., ... Modlin, R. L. (2006). Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science, 311(5768), 1770-3. https://doi.org/10.1126/science.1123933

@article{7b3e1ddcb1e447a4a75790072e943d9d,

title = "Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response",

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.",

keywords = "25-Hydroxyvitamin D3 1-alpha-Hydroxylase, African Americans, Antimicrobial Cationic Peptides, Calcitriol, Cathelicidins, Colony Count, Microbial, Dendritic Cells, Disease Susceptibility, Humans, Immunity, Innate, Macrophages, Monocytes, Mycobacterium tuberculosis, Oligonucleotide Array Sequence Analysis, RNA, Messenger, Receptors, Calcitriol, Steroid Hydroxylases, Toll-Like Receptors, Tuberculosis, Up-Regulation, Vitamin D3 24-Hydroxylase",

author = "Liu, {Philip T} and Steffen Stenger and Huiying Li and Linda Wenzel and Tan, {Belinda H} and Krutzik, {Stephan R} and Ochoa, {Maria Teresa} and J{\"u}rgen Schauber and Kent Wu and Christoph Meinken and Kamen, {Diane L} and Manfred Wagner and Robert Bals and Andreas Steinmeyer and Ulrich Z{\"u}gel and Gallo, {Richard L} and David Eisenberg and Martin Hewison and Hollis, {Bruce W} and Adams, {John S} and Bloom, {Barry R} and Modlin, {Robert L}",

year = "2006",

month = mar,

day = "24",

doi = "10.1126/science.1123933",

language = "English",

volume = "311",

pages = "1770--3",

journal = "Science",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "5768",

}

Liu, PT, Stenger, S, Li, H, Wenzel, L, Tan, BH, Krutzik, SR, Ochoa, MT, Schauber, J, Wu, K, Meinken, C, Kamen, DL, Wagner, M, Bals, R, Steinmeyer, A, Zügel, U, Gallo, RL, Eisenberg, D, Hewison, M, Hollis, BW, Adams, JS, Bloom, BR & Modlin, RL 2006, 'Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response', Science, vol. 311, no. 5768, pp. 1770-3. https://doi.org/10.1126/science.1123933

TY - JOUR

T1 - Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response

AU - Liu, Philip T

AU - Stenger, Steffen

AU - Li, Huiying

AU - Wenzel, Linda

AU - Tan, Belinda H

AU - Krutzik, Stephan R

AU - Ochoa, Maria Teresa

AU - Schauber, Jürgen

AU - Wu, Kent

AU - Meinken, Christoph

AU - Kamen, Diane L

AU - Wagner, Manfred

AU - Bals, Robert

AU - Steinmeyer, Andreas

AU - Zügel, Ulrich

AU - Gallo, Richard L

AU - Eisenberg, David

AU - Hewison, Martin

AU - Hollis, Bruce W

AU - Adams, John S

AU - Bloom, Barry R

AU - Modlin, Robert L

PY - 2006/3/24

Y1 - 2006/3/24

N2 - 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.

AB - 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.

KW - 25-Hydroxyvitamin D3 1-alpha-Hydroxylase

KW - African Americans

KW - Antimicrobial Cationic Peptides

KW - Calcitriol

KW - Cathelicidins

KW - Colony Count, Microbial

KW - Dendritic Cells

KW - Disease Susceptibility

KW - Humans

KW - Immunity, Innate

KW - Macrophages

KW - Monocytes

KW - Mycobacterium tuberculosis

KW - Oligonucleotide Array Sequence Analysis

KW - RNA, Messenger

KW - Receptors, Calcitriol

KW - Steroid Hydroxylases

KW - Toll-Like Receptors

KW - Tuberculosis

KW - Up-Regulation

KW - Vitamin D3 24-Hydroxylase

U2 - 10.1126/science.1123933

DO - 10.1126/science.1123933

M3 - Article

C2 - 16497887

SN - 0036-8075

VL - 311

SP - 1770

EP - 1773

JO - Science

JF - Science

IS - 5768

ER -

Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response

Abstract

Keywords

UN SDGs

Access to Document

Fingerprint

Cite this