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

Research output: Contribution to journalArticlepeer-review


  • 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
  • Bruce W Hollis
  • John S Adams
  • Barry R Bloom
  • Robert L Modlin

Colleges, School and Institutes


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 languageEnglish
Pages (from-to)1770-3
Number of pages4
Issue number5768
Publication statusPublished - 24 Mar 2006


  • 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