title: A bacterial glycan core linked to surface (S)-layer proteins modulates host immunity through Th17 suppression.
abstract: Tannerella forsythia is a pathogen implicated in periodontitis, an inflammatory disease of the tooth-supporting tissues often leading to tooth loss. This key periodontal pathogen is decorated with a unique glycan core O-glycosidically linked to the bacterium's proteinaceous surface (S)-layer lattice and other glycoproteins. Herein, we show that the terminal motif of this glycan core acts to modulate dendritic cell effector functions to suppress T-helper (Th)17 responses. In contrast to the wild-type bacterial strain, infection with a mutant strain lacking the complete S-layer glycan core induced robust Th17 and reduced periodontal bone loss in mice. Our findings demonstrate that surface glycosylation of this pathogen may act to ensure its persistence in the host likely through suppression of Th17 responses. In addition, our data suggest that the bacterium then induces the Toll-like receptor 2-Th2 inflammatory axis that has previously been shown to cause bone destruction. Our study provides a biological basis for pathogenesis and opens opportunities in exploiting bacterial glycans as therapeutic targets against periodontitis and a range of other infectious diseases.
authors.affiliation: Department of Oral Biology, School of Dental Medicine, University at Buffalo, State University of New York, Buffalo, New York, USA.
authors.forename: R P
authors.initials: RP
authors.lastname: Settem
authors.forename: K
authors.initials: K
authors.lastname: Honma
authors.forename: T
authors.initials: T
authors.lastname: Nakajima
authors.forename: C
authors.initials: C
authors.lastname: Phansopa
authors.forename: S
authors.initials: S
authors.lastname: Roy
authors.forename: G P
authors.initials: GP
authors.lastname: Stafford
authors.forename: A
authors.initials: A
authors.lastname: Sharma
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D001419:Bacteria / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism; D005260:Female; D005881:Gingiva / Q000276:immunology / Q000382:microbiology; D006031:Glycosylation; D054884:Host-Pathogen Interactions / Q000276:immunology*; D056747:Immunomodulation; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D009154:Mutation; D016328:NF-kappa B / Q000378:metabolism; D020556:Neutrophil Infiltration / Q000276:immunology; D010010:Osteoclasts / Q000378:metabolism; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D058504:Th17 Cells / Q000276:immunology*; D014774:Virulence / Q000235:genetics / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D016207:Cytokines; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011135:Polysaccharides, Bacterial; C055764:S-layer proteins