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About the Authors:
Sarah A. Tursi
Affiliation: Department of Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States of America
Ernest Y. Lee
Affiliation: Department of Bioengineering, California Nano Systems Institute, University of California, Los Angeles, California, United States of America
ORCID http://orcid.org/0000-0001-5144-2552
Nicole J. Medeiros
Affiliation: Department of Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States of America
ORCID http://orcid.org/0000-0003-4449-2441
Michael H. Lee
Affiliation: Department of Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States of America
Lauren K. Nicastro
Affiliation: Department of Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States of America
Bettina Buttaro
Affiliation: Department of Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States of America
Stefania Gallucci
Affiliation: Department of Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States of America
ORCID http://orcid.org/0000-0003-4737-8003
Ronald Paul Wilson
Affiliation: Department of Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States of America
Gerard C. L. Wong
* E-mail: [email protected] (CT); [email protected] (GCLW)
Affiliations Department of Bioengineering, California Nano Systems Institute, University of California, Los Angeles, California, United States of America, Department of Chemistry and Biochemistry, California Nano Systems Institute, University of California, Los Angeles, California, United States of America
Çagla Tükel
* E-mail: [email protected] (CT); [email protected] (GCLW)
Affiliation: Department of Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, Pennsylvania, United States of America
ORCID http://orcid.org/0000-0001-7073-0226Abstract
Bacterial biofilms are associated with numerous human infections. The predominant protein expressed in enteric biofilms is the amyloid curli, which forms highly immunogenic complexes with DNA. Infection with curli-expressing bacteria or systemic exposure to purified curli-DNA complexes triggers autoimmunity via the generation of type I interferons (IFNs) and anti-double-stranded DNA antibodies. Here, we show that DNA complexed with amyloid curli powerfully stimulates Toll-like receptor 9 (TLR9) through a two-step mechanism. First, the cross beta-sheet structure of curli is bound by cell-surface Toll-like receptor 2 (TLR2), enabling internalization of the complex into endosomes. After internalization, the curli-DNA immune complex binds strongly to endosomal TLR9, inducing production of type I IFNs. Analysis of wild-type and TLR2-deficient macrophages showed that...