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

Science. 2006 Mar 24;311(5768):1770-3. doi: 10.1126/science.1123933. Epub 2006 Feb 23.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / genetics
  • African Americans
  • Antimicrobial Cationic Peptides / biosynthesis
  • Antimicrobial Cationic Peptides / genetics*
  • Antimicrobial Cationic Peptides / metabolism
  • Calcitriol / blood
  • Calcitriol / metabolism*
  • Cathelicidins
  • Colony Count, Microbial
  • Dendritic Cells / microbiology
  • Dendritic Cells / physiology
  • Disease Susceptibility
  • Humans
  • Immunity, Innate*
  • Macrophages / immunology
  • Macrophages / microbiology
  • Macrophages / physiology*
  • Monocytes / microbiology
  • Monocytes / physiology*
  • Mycobacterium tuberculosis / growth & development*
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Calcitriol / genetics
  • Steroid Hydroxylases / genetics
  • Toll-Like Receptors / physiology*
  • Tuberculosis / etiology
  • Tuberculosis / immunology
  • Up-Regulation
  • Vitamin D3 24-Hydroxylase

Substances

  • Antimicrobial Cationic Peptides
  • Cathelicidins
  • RNA, Messenger
  • Receptors, Calcitriol
  • Toll-Like Receptors
  • CAP18 lipopolysaccharide-binding protein
  • Steroid Hydroxylases
  • Vitamin D3 24-Hydroxylase
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Calcitriol