title: Chlamydia muridarum infection-induced destruction of male germ cells and sertoli cells is partially prevented by Chlamydia major outer membrane protein-specific immune CD4 cells.
abstract: Chlamydia trachomatis infections are increasingly prevalent worldwide. Male chlamydial infections are associated with urethritis, epididymitis, and orchitis; however, the role of Chlamydia in prostatitis and male factor infertility remains controversial. Using a model of Chlamydia muridarum infection in male C57BL/6 mice, we investigated the effects of chlamydial infection on spermatogenesis and determined the potential of immune T cells to prevent infection-induced outcomes. Antigen-specific CD4 T cells significantly reduced the infectious burden in the penile urethra, epididymis, and vas deferens. Infection disrupted seminiferous tubules, causing loss of germ cells at 4 and 8 wk after infection, with the most severely affected tubules containing only Sertoli cells. Increased mitotic proliferation, DNA repair, and apoptosis in spermatogonial cells and damaged germ cells were evident in atrophic tubules. Activated caspase 3 (casp3) staining revealed increased (6-fold) numbers of Sertoli cells with abnormal morphology that were casp3 positive in tubules of infected mice, indicating increased levels of apoptosis. Sperm count and motility were both decreased in infected mice, and there was a significant decrease in morphologically normal spermatozoa. Assessment of the spermatogonial stem cell population revealed a decrease in promyelocytic leukemia zinc finger (PLZF)-positive cells in the seminiferous tubules. Interestingly, adoptive transfer of antigen-specific CD4 cells, particularly T-helper 2-like cells, prior to infection prevented these effects in spermatogenesis and Sertoli cells. These data suggest that chlamydial infection adversely affects spermatogenesis and male fertility, and that vaccination can potentially prevent the spread of infection and these adverse outcomes.
authors.affiliation: Priority Research Centres in Chemical Biology and Reproductive Science, School of Environmental & Life Sciences, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Alexander P
authors.initials: AP
authors.lastname: Sobinoff
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Samantha J
authors.initials: SJ
authors.lastname: Dando
authors.affiliation: Priority Research Centres in Chemical Biology and Reproductive Science, School of Environmental & Life Sciences, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Kate A
authors.initials: KA
authors.lastname: Redgrove
authors.affiliation: Priority Research Centres in Chemical Biology and Reproductive Science, School of Environmental & Life Sciences, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Jessie M
authors.initials: JM
authors.lastname: Sutherland
authors.affiliation: Priority Research Centres in Chemical Biology and Reproductive Science, School of Environmental & Life Sciences, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Simone J
authors.initials: SJ
authors.lastname: Stanger
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Charles W
authors.initials: CW
authors.lastname: Armitage
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia.
authors.forename: Peter
authors.initials: P
authors.lastname: Timms
authors.affiliation: Priority Research Centres in Chemical Biology and Reproductive Science, School of Environmental & Life Sciences, University of Newcastle, Newcastle, New South Wales, Australia.
authors.forename: Eileen A
authors.initials: EA
authors.lastname: McLaughlin
authors.affiliation: Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, Queensland, Australia k2.beagley@qut.edu.au.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Beagley
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002690:Chlamydia Infections / Q000276:immunology* / Q000473:pathology; D023502:Chlamydia muridarum / Q000276:immunology* / Q000472:pathogenicity; D019610:Cytoprotection / Q000276:immunology*; D007248:Infertility, Male / Q000382:microbiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012708:Sertoli Cells / Q000502:physiology*; D013091:Spermatogenesis / Q000502:physiology; D013094:Spermatozoa / Q000502:physiology*
chemical_list: D001425:Bacterial Outer Membrane Proteins
keywords: Chlamydia muridarum; Sertoli cell; T cells; spermatogenesis