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Gallo PM , Rapsinski GJ , Wilson RP , Oppong GO , Sriram U , Goulian M , Buttaro B , Caricchio R , Gallucci S , Tukel C
Amyloid-DNA Composites of Bacterial Biofilms Stimulate Autoimmunity
Immunity. 2015 Jun 16;42(6) :1171-84
PMID: 26084027    PMCID: PMC4500125    URL: https://www.ncbi.nlm.nih.gov/pubmed/26084027
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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.
Gallo, Paul M Rapsinski, Glenn J Wilson, R Paul Oppong, Gertrude O Sriram, Uma Goulian, Mark Buttaro, Bettina Caricchio, Roberto Gallucci, Stefania Tukel, Cagla 1R03AI107434/AI/NIAID NIH HHS/United States 1R21AI105370/AI/NIAID NIH HHS/United States R01 AI076423/AI/NIAID NIH HHS/United States R01 AR061569/AR/NIAMS NIH HHS/United States R01-AI076423/AI/NIAID NIH HHS/United States R01-AR061569/AR/NIAMS NIH HHS/United States R03 AI107434/AI/NIAID NIH HHS/United States R03 AR065157/AR/NIAMS NIH HHS/United States R21 AI105370/AI/NIAID NIH HHS/United States Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Immunity. 2015 Jun 16;42(6):1171-84. doi: 10.1016/j.immuni.2015.06.002.