title: Amyloid-DNA Composites of Bacterial Biofilms Stimulate Autoimmunity.
abstract: Research on the human microbiome has established that commensal and pathogenic bacteria can influence obesity, cancer, and autoimmunity through mechanisms mostly unknown. We found that a component of bacterial biofilms, the amyloid protein curli, irreversibly formed fibers with bacterial DNA during biofilm formation. This interaction accelerated amyloid polymerization and created potent immunogenic complexes that activated immune cells, including dendritic cells, to produce cytokines such as type I interferons, which are pathogenic in systemic lupus erythematosus (SLE). When given systemically, curli-DNA composites triggered immune activation and production of autoantibodies in lupus-prone and wild-type mice. We also found that the infection of lupus-prone mice with curli-producing bacteria triggered higher autoantibody titers compared to curli-deficient bacteria. These data provide a mechanism by which the microbiome and biofilm-producing enteric infections may contribute to the progression of SLE and point to a potential molecular target for treatment of autoimmunity.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, USA; Laboratory of Dendritic Cell Biology, School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Gallo
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Glenn J
authors.initials: GJ
authors.lastname: Rapsinski
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, USA.
authors.forename: R Paul
authors.initials: RP
authors.lastname: Wilson
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Gertrude O
authors.initials: GO
authors.lastname: Oppong
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, USA; Laboratory of Dendritic Cell Biology, School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Uma
authors.initials: U
authors.lastname: Sriram
authors.affiliation: Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Goulian
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Bettina
authors.initials: B
authors.lastname: Buttaro
authors.affiliation: Division of Rheumatology, Department of Medicine, School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Caricchio
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, USA; Laboratory of Dendritic Cell Biology, School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, USA.
authors.forename: Stefania
authors.initials: S
authors.lastname: Gallucci
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, Pennsylvania 19140, USA. Electronic address: ctukel@temple.edu.
authors.forename: Çagla
authors.initials: Ç
authors.lastname: Tükel
mesh_terms: D000682:Amyloid / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001426:Bacterial Proteins / Q000276:immunology / Q000378:metabolism*; D018441:Biofilms / Q000254:growth & development; D002478:Cells, Cultured; D004269:DNA, Bacterial / Q000276:immunology / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology*; D004926:Escherichia coli / Q000276:immunology*; D004927:Escherichia coli Infections / Q000276:immunology*; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008814:Mice, Inbred NZB; D058105:Polymerization; D012480:Salmonella Infections / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology*
chemical_list: D000682:Amyloid; D001323:Autoantibodies; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D007370:Interferon Type I