title: Sialylation of Campylobacter jejuni lipo-oligosaccharides: impact on phagocytosis and cytokine production in mice.
abstract: BACKGROUND
  Guillain-Barré syndrome (GBS) is a post-infectious polyradiculoneuropathy, frequently associated with antecedent Campylobacter jejuni (C. jejuni) infection. The presence of sialic acid on C. jejuni lipo-oligosaccharide (LOS) is considered a risk factor for development of GBS as it crucially determines the structural homology between LOS and gangliosides, explaining the induction of cross-reactive neurotoxic antibodies. Sialylated C. jejuni are recognised by TLR4 and sialoadhesin; however, the functional implications of these interactions in vivo are unknown.
  
  
  RESULTS
  In this study we investigated the effects of bacterial sialylation on phagocytosis and cytokine secretion by mouse myeloid cells in vitro and in vivo. Using fluorescently labelled GM1a/GD1a ganglioside-mimicking C. jejuni strains and corresponding (Cst-II-mutant) control strains lacking sialic acid, we show that sialylated C. jejuni was more efficiently phagocytosed in vitro by BM-MΦ, but not by BM-DC. In addition, LOS sialylation increased the production of IL-10, IL-6 and IFN-β by both BM-MΦ and BM-DC. Subsequent in vivo experiments revealed that sialylation augmented the deposition of fluorescent bacteria in splenic DC, but not macrophages. In addition, sialylation significantly amplified the production of type I interferons, which was independent of pDC.
  
  
  CONCLUSIONS
  These results identify novel immune stimulatory effects of C. jejuni sialylation, which may be important in inducing cross-reactive humoral responses that cause GBS.
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
authors.forename: Ruth
authors.initials: R
authors.lastname: Huizinga
authors.forename: Alistair S
authors.initials: AS
authors.lastname: Easton
authors.forename: Anne M
authors.initials: AM
authors.lastname: Donachie
authors.forename: Jim
authors.initials: J
authors.lastname: Guthrie
authors.forename: Wouter
authors.initials: W
authors.lastname: van Rijs
authors.forename: Astrid
authors.initials: A
authors.lastname: Heikema
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.forename: Janneke N
authors.initials: JN
authors.lastname: Samsom
authors.forename: Bart C
authors.initials: BC
authors.lastname: Jacobs
authors.forename: Hugh J
authors.initials: HJ
authors.lastname: Willison
authors.forename: Carl S
authors.initials: CS
authors.lastname: Goodyear
mesh_terms: D000818:Animals; D002169:Campylobacter Infections / Q000473:pathology*; D016123:Campylobacter jejuni / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005732:Gangliosides / Q000378:metabolism; D020275:Guillain-Barre Syndrome / Q000503:physiopathology; D016899:Interferon-beta / Q000378:metabolism; D016753:Interleukin-10 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000378:metabolism; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D010587:Phagocytosis; D013154:Spleen / Q000276:immunology
chemical_list: D016207:Cytokines; D005732:Gangliosides; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016753:Interleukin-10; D016899:Interferon-beta; D019158:N-Acetylneuraminic Acid