title: Variation of Neisseria gonorrhoeae lipooligosaccharide directs dendritic cell-induced T helper responses.
abstract: Gonorrhea is one of the most prevalent sexually transmitted diseases in the world. A naturally occurring variation of the terminal carbohydrates on the lipooligosaccharide (LOS) molecule correlates with altered disease states. Here, we investigated the interaction of different stable gonoccocal LOS phenotypes with human dendritic cells and demonstrate that each variant targets a different set of receptors on the dendritic cell, including the C-type lectins MGL and DC-SIGN. Neisseria gonorrhoeae LOS phenotype C constitutes the first bacterial ligand to be described for the human C-type lectin receptor MGL. Both MGL and DC-SIGN are locally expressed at the male and female genital area, the primary site of N. gonorrhoeae infection. We show that targeting of different C-type lectins with the N. gonorrhoeae LOS variants results in alterations in dendritic cell cytokine secretion profiles and the induction of distinct adaptive CD4(+) T helper responses. Whereas N. gonorrhoeae variant A with a terminal N-acetylglucosamine on its LOS was recognized by DC-SIGN and induced significantly more IL-10 production, phenotype C, carrying a terminal N-acetylgalactosamine, primarily interacted with MGL and skewed immunity towards the T helper 2 lineage. Together, our results indicate that N. gonorrhoeae LOS variation allows for selective manipulation of dendritic cell function, thereby shifting subsequent immune responses in favor of bacterial survival.
authors.affiliation: Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: van Vliet
authors.forename: Liana
authors.initials: L
authors.lastname: Steeghs
authors.forename: Sven C M
authors.initials: SC
authors.lastname: Bruijns
authors.forename: Medi M
authors.initials: MM
authors.lastname: Vaezirad
authors.forename: Christian
authors.initials: C
authors.lastname: Snijders Blok
authors.forename: Jésus A
authors.initials: JA
authors.lastname: Arenas Busto
authors.forename: Marcel
authors.initials: M
authors.lastname: Deken
authors.forename: Jos P M
authors.initials: JP
authors.lastname: van Putten
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
mesh_terms: D000818:Animals; D000940:Antigenic Variation / Q000276:immunology*; D016466:CHO Cells; D002240:Carbohydrate Sequence; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D003713:Dendritic Cells / Q000276:immunology*; D005260:Female; D006031:Glycosylation; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D037181:Lectins, C-Type / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology*; D008297:Male; D008954:Models, Biological; D008969:Molecular Sequence Data; D009344:Neisseria gonorrhoeae / Q000276:immunology*; D010641:Phenotype; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
chemical_list: D037181:Lectins, C-Type; D008070:Lipopolysaccharides; C023023:lipid-linked oligosaccharides