title: Sialylation of Campylobacter jejuni endotoxin promotes dendritic cell-mediated B cell responses through CD14-dependent production of IFN-β and TNF-α.
abstract: Campylobacter jejuni is the most common bacterial cause of human gastroenteritis and often precedes development of Guillain-Barré syndrome (GBS), a life-threatening paralytic disease. The incorporation of the carbohydrate sialic acid into C. jejuni lipooligosaccharides (LOS) is associated with increased severity of gastroenteritis and with induction of GBS; however, the underlying mechanisms remain completely unknown. In this study, we demonstrate that sialic acids in C. jejuni endotoxin enhance the rapid production of IFN-β and TNF-α by human dendritic cells (DCs). Using neutralizing Abs and receptors it was shown that these DC-derived cytokines promote the proliferation of human mucosal B cells in a T cell-independent manner. The production of both IFN-β and TNF-α by DCs in response to LOS requires CD14, and the amplified response of DCs to sialylated C. jejuni LOS is CD14 dependent. Together, these results indicate that sialylation of C. jejuni LOS increases DC activation and promotes subsequent B cell responses through CD14-driven production of IFN-β and TNF-α. This enhanced DC/B cell response may explain the increased pathogenicity of sialylated C. jejuni and may be key to the initiation of B cell-mediated autoimmunity in GBS.
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, 3000 CA Rotterdam, The Netherlands;
authors.forename: Ruth
authors.initials: R
authors.lastname: Huizinga
authors.forename: Wouter
authors.initials: W
authors.lastname: van Rijs
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Bajramovic
authors.forename: Mark L
authors.initials: ML
authors.lastname: Kuijf
authors.forename: Jon D
authors.initials: JD
authors.lastname: Laman
authors.forename: Janneke N
authors.initials: JN
authors.lastname: Samsom
authors.forename: Bart C
authors.initials: BC
authors.lastname: Jacobs
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D002169:Campylobacter Infections / Q000150:complications / Q000276:immunology*; D016123:Campylobacter jejuni / Q000276:immunology*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D004731:Endotoxins / Q000737:chemistry / Q000276:immunology; D005759:Gastroenteritis / Q000209:etiology / Q000276:immunology*; D020275:Guillain-Barre Syndrome / Q000209:etiology / Q000276:immunology*; D006801:Humans; D016899:Interferon-beta / Q000378:metabolism; D007413:Intestinal Mucosa / Q000473:pathology; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008213:Lymphocyte Activation; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004731:Endotoxins; D018950:Lipopolysaccharide Receptors; D014409:Tumor Necrosis Factor-alpha; D016899:Interferon-beta; D019158:N-Acetylneuraminic Acid