title: Effect of Chlamydia trachomatis infection and subsequent tumor necrosis factor alpha secretion on apoptosis in the murine genital tract.
abstract: The pathology observed during Chlamydia infection is due initially to localized tissue damage caused by the infection itself, followed by deleterious host inflammatory responses that lead to permanent scarring. We have recently reported that the infection by Chlamydia in vitro results in apoptosis of epithelial cells and macrophages and that infected monocytes secrete the proinflammatory cytokine interleukin-1beta. At the same time, proinflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha) can also trigger apoptosis of susceptible cells. To study the possible relationship between Chlamydia trachomatis infection and apoptosis in vivo, we used the terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling technique to determine whether infection may cause apoptosis in the genital tract of mice and, conversely, whether cytokines produced during the inflammatory response may modulate the level of apoptosis. Our results demonstrate that infected cells in the endocervix at day 2 or 7 after infection are sometimes apoptotic, although there was not a statistically significant change in the number of apoptotic cells in the endocervix. However, large clumps of apoptotic infected cells were observed in the lumen, suggesting that apoptotic cells may be shed from the endocervix. Moreover, there was a large increase in the number of apoptotic cells in the uterine horns and oviducts after 2 or 7 days of infection, which was accompanied by obvious signs of upper tract pathology. Interestingly, depletion of TNF-alpha led to a decrease in the level of apoptosis in the uterine horns and oviducts of animals infected for 7 days, suggesting that the inflammatory cytokines may exert part of their pathological effect via apoptosis in infected tissues.
authors.affiliation: Unité de Biologie des Interactions Cellulaires, CNRS URA 1960, Institut Pasteur, 75724 Paris Cedex 15, France.
authors.forename: J L
authors.initials: JL
authors.lastname: Perfettini
authors.forename: T
authors.initials: T
authors.lastname: Darville
authors.forename: G
authors.initials: G
authors.lastname: Gachelin
authors.forename: P
authors.initials: P
authors.lastname: Souque
authors.forename: M
authors.initials: M
authors.lastname: Huerre
authors.forename: A
authors.initials: A
authors.lastname: Dautry-Varsat
authors.forename: D M
authors.initials: DM
authors.lastname: Ojcius
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002584:Cervix Uteri / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D002690:Chlamydia Infections / Q000276:immunology*; D002692:Chlamydia trachomatis / Q000276:immunology*; D053938:DNA Fragmentation; D004847:Epithelial Cells / Q000382:microbiology / Q000473:pathology; D005187:Fallopian Tubes / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology; D005260:Female; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D020287:In Situ Nick-End Labeling; D007375:Interleukin-1 / Q000096:biosynthesis; D051379:Mice; D008810:Mice, Inbred C57BL; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology / Q000502:physiology; D014599:Uterus / Q000378:metabolism* / Q000382:microbiology / Q000473:pathology
chemical_list: D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha