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

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 D 3 . VDR −/− mice exhibited significantly higher bacterial loading than wild-type VDR +/+ mice ( P +/+ mice. Monocytes and neutrophils were more numerous in the uterus and oviduct of VDR −/− mice than in VDR +/+ mice ( P 3 decreased the infectivity of C. muridarum ( P 3 . 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.