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Cervical mucins carry alpha(1,2)fucosylated glycans that partly protect from experimental vaginal candidiasis.

Artikel i vetenskaplig tidskrift
Författare Steven E Domino
Elizabeth A Hurd
Kristina A Thomsson
David M Karnak
Jessica Holmén Larsson
Elisabeth Thomsson
Malin Bäckström
Gunnar C. Hansson
Publicerad i Glycoconjugate journal
Volym 26
Nummer/häfte 9
Sidor 1125-34
ISSN 1573-4986
Publiceringsår 2009
Publicerad vid Institutionen för biomedicin, avdelningen för medicinsk kemi och cellbiologi
Sidor 1125-34
Språk en
Länkar dx.doi.org/10.1007/s10719-009-9234-...
Ämnesord Animals, Candida albicans, growth & development, Candidiasis, Vulvovaginal, chemically induced, pathology, prevention & control, Carbohydrate Sequence, Cell Adhesion, Cervix Mucus, metabolism, microbiology, Colony Count, Microbial, Disease Susceptibility, Epithelial Cells, enzymology, microbiology, pathology, Epitopes, immunology, Female, Fucose, metabolism, Fucosyltransferases, deficiency, metabolism, Hysterectomy, Mice, Mice, Inbred C57BL, Molecular Sequence Data, Mucin-1, metabolism, Mucins, metabolism, Polysaccharides, metabolism, Recombinant Proteins, metabolism, Vaginal Smears
Ämneskategorier Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)

Sammanfattning

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.

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