title: Campylobacter jejuni lipooligosaccharides modulate dendritic cell-mediated T cell polarization in a sialic acid linkage-dependent manner.
abstract: Carbohydrate mimicry between Campylobacter jejuni lipooligosaccharides (LOS) and host neural gangliosides plays a crucial role in the pathogenesis of Guillain-Barré syndrome (GBS). Campylobacter jejuni LOS may mimic various gangliosides, which affects the immunogenicity and the type of neurological deficits in GBS patients. Previous studies have shown the interaction of LOS with sialic acid-specific siglec receptors, although the functional consequences remain unknown. Cells that express high levels of siglecs include dendritic cells (DCs), which are crucial for initiation and differentiation of immune responses. We confirm that α2,3-sialylated GD1a/GM1a mimic and α2,8-sialylated GD1c mimic LOS structures interact with recombinant Sn and siglec-7, respectively. Although the linkage of the terminal sialic acid of LOS did not regulate expression of DC maturation markers, it displayed clear opposite expression levels of interleukin-12 (IL-12) and OX40L, molecules involved in DC-mediated Th cell differentiation. Accordingly, targeting DC-expressed siglec-7 with α2,8-linked sialylated LOS resulted in Th1 responses, whereas Th2 responses were induced by targeting with LOS containing α2,3-linked sialic acid. Thus, our data demonstrate for the first time that depending on the sialylated composition of Campylobacter jejuni LOS, specific Th differentiation programs are initiated, possibly through targeting of distinct DC-expressed siglecs.
authors.affiliation: Department of Molecular Cell Biology and Immunology, Vrije Universiteit Medical Center, PO Box 7057, 1007MB Amsterdam, Netherlands.
authors.forename: Marieke
authors.initials: M
authors.lastname: Bax
authors.forename: Mark L
authors.initials: ML
authors.lastname: Kuijf
authors.forename: Astrid P
authors.initials: AP
authors.lastname: Heikema
authors.forename: Wouter
authors.initials: W
authors.lastname: van Rijs
authors.forename: Sven C M
authors.initials: SC
authors.lastname: Bruijns
authors.forename: Juan J
authors.initials: JJ
authors.lastname: García-Vallejo
authors.forename: Paul R
authors.initials: PR
authors.lastname: Crocker
authors.forename: Bart C
authors.initials: BC
authors.lastname: Jacobs
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: van Vliet
authors.forename: Yvette
authors.initials: Y
authors.lastname: van Kooyk
mesh_terms: D016123:Campylobacter jejuni / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D002236:Carbohydrate Conformation; D002454:Cell Differentiation; D002460:Cell Line; D016764:Cell Polarity; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D005677:G(M1) Ganglioside / Q000737:chemistry; D005732:Gangliosides / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D020275:Guillain-Barre Syndrome / Q000276:immunology / Q000382:microbiology; D057809:HEK293 Cells; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D037102:Lectins / Q000378:metabolism; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism*; D018716:Molecular Mimicry; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D053278:OX40 Ligand / Q000096:biosynthesis / Q000235:genetics; D016133:Polymerase Chain Reaction; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
chemical_list: D005732:Gangliosides; D037102:Lectins; D008070:Lipopolysaccharides; D053278:OX40 Ligand; D063265:Sialic Acid Binding Immunoglobulin-like Lectins; C023023:lipid-linked oligosaccharides; C072151:ganglioside, GD1c; C021298:ganglioside, GD1a; D018664:Interleukin-12; D005677:G(M1) Ganglioside; D019158:N-Acetylneuraminic Acid