title: Sialylation of Porphyromonas gingivalis LPS and its effect on bacterial-host interactions.
abstract: Porphyromonas gingivalis produces different LPS isoforms with significant structural variations of their lipid A and O-antigen moieties that can affect its pro-inflammatory and bone-resorbing potential. We show here, for the first time, that P. gingivalis LPS isolated from W83 strain is highly sialylated and possesses significantly reduced inflammatory potential compared with less sialylated ATCC 33277 strain LPS. Nevertheless, the reduction in the endotoxin activity is not mediated by the presence of sialic acid LPS moieties as the sialic acid-free LPS produced by the mutant W83 strain exhibits a similar inflammatory potential to the wild type strain. Furthermore, our findings suggest that the interaction between the sialic acid LPS moieties and the inhibitory CD33 receptor is prevented by endogenously expressed sialic acid on the surface of THP-1 cells that cannot be out-competed by sialic acid containing P. gingivalis LPS. The present study also highlights the importance of endogenous sialic acid as a 'self-associated molecular pattern' and CD33 receptors in modulation of innate immune response as human gingival fibroblasts, which do not express CD33 receptors, and desialylated THP-1 cells have both been found to have much higher spontaneous IL-8 production than naïve THP-1 cells.
authors.affiliation: 1 Plymouth University, Peninsula Schools of Medicine and Dentistry, Plymouth, UK.
authors.forename: Svetislav S
authors.initials: SS
authors.lastname: Zaric
authors.affiliation: 2 Queen's University Belfast, Centre for Dentistry, Belfast, UK.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Lappin
authors.affiliation: 3 Queen's University Belfast, Centre for Experimental Medicine, Belfast, UK.
authors.forename: Catherine R
authors.initials: CR
authors.lastname: Fulton
authors.affiliation: 3 Queen's University Belfast, Centre for Experimental Medicine, Belfast, UK.
authors.forename: Fionnuala T
authors.initials: FT
authors.lastname: Lundy
authors.affiliation: 4 University of Ulster, School of Biomedical Science, Coleraine, UK.
authors.forename: Wilson A
authors.initials: WA
authors.lastname: Coulter
authors.affiliation: 2 Queen's University Belfast, Centre for Dentistry, Belfast, UK.
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Irwin
mesh_terms: D016866:Bacteroidaceae Infections / Q000276:immunology*; D002460:Cell Line; D005347:Fibroblasts / Q000276:immunology* / Q000382:microbiology; D005881:Gingiva / Q000473:pathology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D016209:Interleukin-8 / Q000378:metabolism; D008050:Lipid A / Q000737:chemistry; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology*; D009000:Monocytes / Q000276:immunology* / Q000382:microbiology; D009154:Mutation / Q000235:genetics; D019158:N-Acetylneuraminic Acid / Q000737:chemistry / Q000378:metabolism*; D019081:O Antigens / Q000737:chemistry; D010510:Periodontal Diseases / Q000276:immunology*; D016966:Porphyromonas gingivalis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011499:Protein Processing, Post-Translational; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000378:metabolism
chemical_list: D016209:Interleukin-8; D008050:Lipid A; D008070:Lipopolysaccharides; D019081:O Antigens; D063268:Sialic Acid Binding Ig-like Lectin 3; D019158:N-Acetylneuraminic Acid
keywords: Inflammation; LPS; Porphyromonas gingivalis; periodontal diseases; sialic acid