title: Toll-like receptor 2 and NLRP3 cooperate to recognize a functional bacterial amyloid, curli.
abstract: Amyloids are proteins with cross-β-sheet structure that contribute to pathology and inflammation in complex human diseases, including Alzheimer's disease, Parkinson's disease, type II diabetes, and secondary amyloidosis. Bacteria also produce amyloids as a component of their extracellular matrix during biofilm formation. Recently, several human amyloids were shown to activate the NLRP3 inflammasome, leading to the activation of caspase 1 and production of interleukin 1β (IL-1β). In this study, we investigated the activation of the NLRP3 inflammasome by bacterial amyloids using curli fibers, produced by Salmonella enterica serovar Typhimurium and Escherichia coli. Here, we show that curli fibers activate the NLRP3 inflammasome, leading to the production of IL-1β via caspase 1 activation. Investigation of the underlying mechanism revealed that activation of Toll-like receptor 2 (TLR2) by curli fibers is critical in the generation of IL-1β. Interestingly, activation of the NLRP3 inflammasome by curli fibers or by amyloid β of Alzheimer's disease does not cause cell death in macrophages. Overall, these data identify a cross talk between TLR2 and NLRP3 in response to the bacterial amyloid curli and generation of IL-1β as a product of this interaction.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, Pennsylvania, USA.
authors.forename: Glenn J
authors.initials: GJ
authors.lastname: Rapsinski
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Meghan A
authors.initials: MA
authors.lastname: Wynosky-Dolfi
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, Pennsylvania, 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, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Tursi
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, Pennsylvania, USA.
authors.forename: R Paul
authors.initials: RP
authors.lastname: Wilson
authors.affiliation: Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Igor E
authors.initials: IE
authors.lastname: Brodsky
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, Temple University, Philadelphia, Pennsylvania, USA ctukel@temple.edu.
authors.forename: Çagla
authors.initials: Ç
authors.lastname: Tükel
mesh_terms: D000682:Amyloid / Q000276:immunology*; D016229:Amyloid beta-Peptides / Q000276:immunology; D000818:Animals; D001426:Bacterial Proteins / Q000276:immunology*; D001854:Bone Marrow Cells; D002352:Carrier Proteins / Q000276:immunology*; D020170:Caspase 1 / Q000096:biosynthesis; D002478:Cells, Cultured; D004926:Escherichia coli / Q000378:metabolism; D058847:Inflammasomes / Q000276:immunology; D053583:Interleukin-1beta / Q000096:biosynthesis*; D008264:Macrophages; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D012486:Salmonella typhimurium / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000276:immunology*
chemical_list: D000682:Amyloid; D016229:Amyloid beta-Peptides; D001426:Bacterial Proteins; D002352:Carrier Proteins; C587672:IL1B protein, mouse; D058847:Inflammasomes; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; C077481:Crl protein, Bacteria; D020170:Caspase 1