title: Cervical mucins carry alpha(1,2)fucosylated glycans that partly protect from experimental vaginal candidiasis.
abstract: Cervical mucins are glycosylated proteins that form a protective cervical mucus. To understand the role of mucin glycans in Candida albicans infection, oligosaccharides from mouse cervical mucins were analyzed by liquid chromatography-mass spectrometry. Cervical mucins carry multiple alpha(1-2)fucosylated glycans, but alpha(1,2)fucosyltransferase Fut2-null mice are devoid of these epitopes. Epithelial cells in vaginal lavages from Fut2-null mice lacked Ulex europaeus agglutinin-1 (UEA-I) staining for alpha(1-2)fucosylated glycans. Hysterectomy to remove cervical mucus eliminated UEA-I and acid mucin staining in vaginal epithelial cells from wild type mice indicating the cervix as the source of UEA-I positive epithelial cells. To assess binding of alpha(1-2) fucosylated glycans on C. albicans infection, an in vitro adhesion assay was performed with vaginal epithelial cells from wild type and Fut2-null mice. Vaginal epithelial cells from Fut2-null mice were found to bind increased numbers of C. albicans compared to vaginal epithelial cells obtained from wild type mice. Hysterectomy lessened the difference between Fut2-null and wild type mice in binding of C. ablicans in vitro and susceptibility to experimental C. albicans vaginitis in vivo. We generated a recombinant fucosylated MUC1 glycanpolymer to test whether the relative protection of wild type mice compared to Fut2-null mice could be mimicked with exogenous mucin. While a small portion of the recombinant MUC1 epitopes displayed alpha(1-2)fucosylated glycans, the predominant epitopes were sialylated due to endogenous sialyltransferases in the cultured cells. Intravaginal instillation of recombinant MUC1 glycanpolymer partially reduced experimental yeast vaginitis suggesting that a large glycanpolymer, with different glycan epitopes, may affect fungal burden.
authors.affiliation: Department of Obstetrics and Gynecology, Cellular and Molecular Biology Program, University of Michigan Medical Center, Ann Arbor, MI, 48109, USA. sedomino@med.umich.edu
authors.forename: Steven E
authors.initials: SE
authors.lastname: Domino
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Hurd
authors.forename: Kristina A
authors.initials: KA
authors.lastname: Thomsson
authors.forename: David M
authors.initials: DM
authors.lastname: Karnak
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Holmén Larsson
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Thomsson
authors.forename: Malin
authors.initials: M
authors.lastname: Bäckström
authors.forename: Gunnar C
authors.initials: GC
authors.lastname: Hansson