Chlamydial infection in vitamin D receptor knockout mice is more intense and prolonged than in wild-type mice

J Steroid Biochem Mol Biol. 2013 May;135:7-14. doi: 10.1016/j.jsbmb.2012.11.002. Epub 2012 Nov 29.

Abstract

Vitamin D hormone (1,25-dihydroxyvitamin D) is involved in innate immunity and induces host defense peptides in epithelial cells, suggesting its involvement in mucosal defense against infections. Chlamydia trachomatis is a major cause of bacterial sexually transmitted disease worldwide. We tested the hypothesis that the vitamin D endocrine system would attenuate chlamydial infection. Vitamin D receptor knock-out mice (VDR(-/-)) and wild-type mice (VDR(+/+)) were infected with 10(3) inclusion forming units of Chlamydia muridarum and cervical epithelial cells (HeLa cells) were infected with C. muridarum at multiplicity of infection 5:1 in the presence and absence of 1,25-dihydroxyvitamin D3. VDR(-/-) mice exhibited significantly higher bacterial loading than wild-type VDR(+/+) mice (P<0.01) and cleared the chlamydial infection in 39 days, compared with 18 days for VDR(+/+) mice. Monocytes and neutrophils were more numerous in the uterus and oviduct of VDR(-/-) mice than in VDR(+/+) mice (P<0.05) at d 45 after infection. Pre-treatment of HeLa cells with 10nM or 100nM 1,25-dihydroxyvitamin D3 decreased the infectivity of C. muridarum (P<0.001). Several differentially expressed protein spots were detected by proteomic analysis of chlamydial-infected HeLa cells pre-treated with 1,25-dihydroxyvitamin D3. Leukocyte elastase inhibitor (LEI), an anti-inflammatory protein, was up-regulated. Expression of LEI in the ovary and oviduct of infected VDR(+/+) mice was greater than that of infected VDR(-/-) mice. We conclude that the vitamin D endocrine system reduces the risk for prolonged chlamydial infections through regulation of several proteins and that LEI is involved in its anti-inflammatory activity.

Publication types

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

MeSH terms

  • Animals
  • Bacterial Load
  • Calcitriol / pharmacology*
  • Cell Line, Tumor
  • Chlamydia muridarum / pathogenicity*
  • Chlamydiaceae Infections / immunology
  • Chlamydiaceae Infections / metabolism*
  • Chlamydiaceae Infections / microbiology
  • Chlamydiaceae Infections / pathology
  • Female
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • Leukocyte Elastase / antagonists & inhibitors
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Proteome
  • Receptors, Calcitriol / deficiency
  • Receptors, Calcitriol / genetics
  • Receptors, Calcitriol / physiology*
  • Serpins / metabolism

Substances

  • Proteome
  • Receptors, Calcitriol
  • Serpinb1a protein, mouse
  • Serpins
  • Leukocyte Elastase
  • Calcitriol