title: Modeling the transcriptome of genital tract epithelial cells and macrophages in healthy mucosa versus mucosa inflamed by Chlamydia muridarum infection.
abstract: Chlamydia trachomatis urogenital serovars are intracellular bacteria that parasitize human reproductive tract epithelium. As the principal cell type supporting bacterial replication, epithelial cells are central to Chlamydia immunobiology initially as sentries and innate defenders, and subsequently as collaborators in adaptive immunity-mediated bacterial clearance. In asymptomatic individuals who do not seek medical care a decisive struggle between C. trachomatis and host defenses occurs at the epithelial interface. For this study, we modeled the immunobiology of epithelial cells and macrophages lining healthy genital mucosa and inflamed/infected mucosa during the transition from innate to adaptive immunity. Upper reproductive tract epithelial cell line responses were compared to bone marrow-derived macrophages utilizing gene expression microarray technology. Those comparisons showed minor differences in the intrinsic innate defenses of macrophages and epithelial cells. Major lineage-specific differences in immunobiology relate to epithelial collaboration with adaptive immunity including an epithelial requirement for inflammatory cytokines to express MHC class II molecules, and a paucity and imbalance between costimulatory and coinhibitory ligands on epithelial cells that potentially limits sterilizing immunity (replication termination) to Chlamydia-specific T cells activated with limited or unconventional second signals.
authors.affiliation: Department of Medicine, Indiana University, Indianapolis, IN 46202, USA raymond.johnson@yale.edu.
authors.forename: Raymond M
authors.initials: RM
authors.lastname: Johnson
authors.affiliation: Department of Microbiology, Indiana University, Indianapolis, IN 46202, USA.
authors.forename: Micah S
authors.initials: MS
authors.lastname: Kerr
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D002460:Cell Line; D002690:Chlamydia Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D023502:Chlamydia muridarum / Q000254:growth & development*; D004847:Epithelial Cells / Q000382:microbiology / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D008264:Macrophages / Q000382:microbiology / Q000502:physiology*; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D008954:Models, Biological; D009092:Mucous Membrane / Q000166:cytology / Q000382:microbiology; D060737:Reproductive Tract Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology
keywords: Chlamydia; cytokines; epithelial cells; gene expression; macrophages; micro array