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

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 103 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 10 nM or 100 nM 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.

► Vitamin D receptor knock-out mice were infected with Chlamydia muridarum. ► Chlamydial infection was more intense and prolonged in vitamin D receptor knock-out mice. ► Pre-treatment of HeLa cells with vitamin D hormone reduced chlamydial infectivity. ► Vitamin D receptor is involved in immuno-regulation of chlamydial infection. ► Leukocyte elastase inhibitor may be involved in the anti-inflammatory action.