title: Trichomonas vaginalis lipophosphoglycan triggers a selective upregulation of cytokines by human female reproductive tract epithelial cells.
abstract: Trichomonas vaginalis is one of the most common nonviral sexually transmitted human infections and, worldwide, has been linked to increased incidence of human immunodeficiency virus type 1 transmission, preterm delivery, low birth weight, cervical cancer, and vaginitis. The molecular pathways that are important in initiating host inflammatory and immune responses to T. vaginalis are poorly understood. Here we report interactions of human cervicovaginal epithelial cells with the most abundant cell surface glycoconjugate of the parasite, the T. vaginalis lipophosphoglycan (LPG). Purified LPG mediated the adhesion of parasites to human vaginal epithelial cells in a dose-dependent manner. Furthermore, T. vaginalis LPG (but not LPG from Tritrichomonas foetus, the causative agent of bovine trichomoniasis) induced a selective upregulation of chemotactic cytokines by human endocervical, ectocervical, and vaginal epithelial cells, which do not express Toll-like receptor 4/MD2. The T. vaginalis LPG triggered interleukin 8 (IL-8), which promotes the adhesion and transmigration of neutrophils across the endothelium, and macrophage inflammatory protein 3alpha, which is a chemoattractant for immune cells and is essential for dendritic cell maturation. These effects were dose dependent and sustained in the absence of cytotoxicity and IL-1beta release and utilized, at least in part, a signaling pathway independent from the Toll-like/IL-1 receptor adaptor protein MyD88.
authors.affiliation: Laboratory of Genital Tract Biology, Department of Obstetrics, Gynecology and Reproductive Biology, Harvard Medical School, Brigham and Women's Hospital, 221 Longwood Avenue, RF468, Boston, MA 02115, USA. rfichorova@partners.org
authors.forename: Raina N
authors.initials: RN
authors.lastname: Fichorova
authors.forename: Radiana T
authors.initials: RT
authors.lastname: Trifonova
authors.forename: Robert O
authors.initials: RO
authors.lastname: Gilbert
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Costello
authors.forename: Gary R
authors.initials: GR
authors.lastname: Hayes
authors.forename: John J
authors.initials: JJ
authors.lastname: Lucas
authors.forename: Bibhuti N
authors.initials: BN
authors.lastname: Singh
mesh_terms: D000818:Animals; D002417:Cattle; D002584:Cervix Uteri / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000378:metabolism; D002633:Chemotaxis; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects / Q000276:immunology; D005260:Female; D006028:Glycosphingolipids / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D019402:Macrophage Inflammatory Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D000267:Tissue Adhesions / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014246:Trichomonas vaginalis / Q000378:metabolism / Q000472:pathogenicity*; D015854:Up-Regulation; D014621:Vagina / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
chemical_list: C108355:CCL20 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D016207:Cytokines; D006028:Glycosphingolipids; D016209:Interleukin-8; D019402:Macrophage Inflammatory Proteins; D008562:Membrane Glycoproteins; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human; D051197:Toll-Like Receptor 4; C008290:lipophosphonoglycan