title: 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 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.
authors.affiliation: Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA. qhe@msm.edu
authors.forename: Qing
authors.initials: Q
authors.lastname: He
authors.forename: Godwin A
authors.initials: GA
authors.lastname: Ananaba
authors.forename: John
authors.initials: J
authors.lastname: Patrickson
authors.forename: Sidney
authors.initials: S
authors.lastname: Pitts
authors.forename: Yeming
authors.initials: Y
authors.lastname: Yi
authors.forename: Fengxia
authors.initials: F
authors.lastname: Yan
authors.forename: Francis O
authors.initials: FO
authors.lastname: Eko
authors.forename: Deborah
authors.initials: D
authors.lastname: Lyn
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Black
authors.forename: Joseph U
authors.initials: JU
authors.lastname: Igietseme
authors.forename: Myrtle
authors.initials: M
authors.lastname: Thierry-Palmer
mesh_terms: D000818:Animals; D058491:Bacterial Load; D002117:Calcitriol / Q000494:pharmacology*; D045744:Cell Line, Tumor; D023502:Chlamydia muridarum / Q000472:pathogenicity*; D002694:Chlamydiaceae Infections / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D019272:Leukocyte Elastase / Q000037:antagonists & inhibitors; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020543:Proteome; D018167:Receptors, Calcitriol / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015843:Serpins / Q000378:metabolism
chemical_list: D020543:Proteome; D018167:Receptors, Calcitriol; C522950:Serpinb1a protein, mouse; D015843:Serpins; D019272:Leukocyte Elastase; D002117:Calcitriol