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Miller AL , Pasternak JA , Medeiros NJ , Nicastro LK , Tursi SA , Hansen EG , Krochak R , Sokaribo AS , MacKenzie KD , Palmer MB , Herman DJ , Watson NL , Zhang Y , Wilson HL , Wilson RP , White AP , Tükel Ç
In vivo synthesis of bacterial amyloid curli contributes to joint inflammation during S. Typhimurium infection
PLoS Pathog. 2020 Jul;16(7) :e1008591
PMID: 32645118    PMCID: PMC7347093    URL: https://www.ncbi.nlm.nih.gov/pubmed/32645118
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Reactive arthritis, an autoimmune disorder, occurs following gastrointestinal infection with invasive enteric pathogens, such as Salmonella enterica. Curli, an extracellular, bacterial amyloid with cross beta-sheet structure can trigger inflammatory responses by stimulating pattern recognition receptors. Here we show that S. Typhimurium produces curli amyloids in the cecum and colon of mice after natural oral infection, in both acute and chronic infection models. Production of curli was associated with an increase in anti-dsDNA autoantibodies and joint inflammation in infected mice. The negative impacts on the host appeared to be dependent on invasive systemic exposure of curli to immune cells. We hypothesize that in vivo synthesis of curli contributes to known complications of enteric infections and suggest that cross-seeding interactions can occur between pathogen-produced amyloids and amyloidogenic proteins of the host.
1553-7374 Miller, Amanda L Pasternak, J Alex Orcid: 0000-0001-8596-3057 Medeiros, Nicole J Nicastro, Lauren K Orcid: 0000-0001-7676-3694 Tursi, Sarah A Hansen, Elizabeth G Orcid: 0000-0003-1133-8093 Krochak, Ryan Sokaribo, Akosiererem S Orcid: 0000-0002-3377-8367 MacKenzie, Keith D Orcid: 0000-0003-2568-6005 Palmer, Melissa B Orcid: 0000-0001-8401-0860 Herman, Dakoda J Orcid: 0000-0003-1397-7198 Watson, Nikole L Zhang, Yi Wilson, Heather L Orcid: 0000-0002-1261-0901 Wilson, R Paul White, Aaron P Orcid: 0000-0003-2746-5265 Tükel, Çagla Orcid: 0000-0001-7073-0226 Journal Article PLoS Pathog. 2020 Jul 9;16(7):e1008591. doi: 10.1371/journal.ppat.1008591. eCollection 2020 Jul.