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Assembly of ordered DNA-curli fibril complexes during Salmonella biofilm formation correlates with strengths of the type I interferon and autoimmune responses

Deposition of human amyloids is associated with complex human diseases such as Alzheimer’s and Parkinson’s. Amyloid proteins are also produced by bacteria. The bacterial amyloid curli, found in the extracellular matrix of both commensal and pathogenic enteric bacterial biofilms, forms complexes with...

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Autores principales: Nicastro, Lauren K., de Anda, Jaime, Jain, Neha, Grando, Kaitlyn C. M., Miller, Amanda L., Bessho, Shingo, Gallucci, Stefania, Wong, Gerard C. L., Tükel, Çagla
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9380926/
https://www.ncbi.nlm.nih.gov/pubmed/35972973
http://dx.doi.org/10.1371/journal.ppat.1010742
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author Nicastro, Lauren K.
de Anda, Jaime
Jain, Neha
Grando, Kaitlyn C. M.
Miller, Amanda L.
Bessho, Shingo
Gallucci, Stefania
Wong, Gerard C. L.
Tükel, Çagla
author_facet Nicastro, Lauren K.
de Anda, Jaime
Jain, Neha
Grando, Kaitlyn C. M.
Miller, Amanda L.
Bessho, Shingo
Gallucci, Stefania
Wong, Gerard C. L.
Tükel, Çagla
author_sort Nicastro, Lauren K.
collection PubMed
description Deposition of human amyloids is associated with complex human diseases such as Alzheimer’s and Parkinson’s. Amyloid proteins are also produced by bacteria. The bacterial amyloid curli, found in the extracellular matrix of both commensal and pathogenic enteric bacterial biofilms, forms complexes with extracellular DNA, and recognition of these complexes by the host immune system may initiate an autoimmune response. Here, we isolated early intermediate, intermediate, and mature curli fibrils that form throughout the biofilm development and investigated the structural and pathogenic properties of each. Early intermediate aggregates were smaller than intermediate and mature curli fibrils, and circular dichroism, tryptophan, and thioflavin T analyses confirmed the establishment of a beta-sheet secondary structure as the curli conformations matured. Intermediate and mature curli fibrils were more immune stimulatory than early intermediate fibrils in vitro. The intermediate curli was cytotoxic to macrophages independent of Toll-like receptor 2. Mature curli fibrils had the highest DNA content and induced the highest levels of Isg15 expression and TNFα production in macrophages. In mice, mature curli fibrils induced the highest levels of anti-double-stranded DNA autoantibodies. The levels of autoantibodies were higher in autoimmune-prone NZBWxF/1 mice than wild-type C57BL/6 mice. Chronic exposure to all curli forms led to significant histopathological changes and synovial proliferation in the joints of autoimmune-prone mice; mature curli was the most detrimental. In conclusion, curli fibrils, generated during biofilm formation, cause pathogenic autoimmune responses that are stronger when curli complexes contain higher levels of DNA and in mice predisposed to autoimmunity.
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spelling pubmed-93809262022-08-17 Assembly of ordered DNA-curli fibril complexes during Salmonella biofilm formation correlates with strengths of the type I interferon and autoimmune responses Nicastro, Lauren K. de Anda, Jaime Jain, Neha Grando, Kaitlyn C. M. Miller, Amanda L. Bessho, Shingo Gallucci, Stefania Wong, Gerard C. L. Tükel, Çagla PLoS Pathog Research Article Deposition of human amyloids is associated with complex human diseases such as Alzheimer’s and Parkinson’s. Amyloid proteins are also produced by bacteria. The bacterial amyloid curli, found in the extracellular matrix of both commensal and pathogenic enteric bacterial biofilms, forms complexes with extracellular DNA, and recognition of these complexes by the host immune system may initiate an autoimmune response. Here, we isolated early intermediate, intermediate, and mature curli fibrils that form throughout the biofilm development and investigated the structural and pathogenic properties of each. Early intermediate aggregates were smaller than intermediate and mature curli fibrils, and circular dichroism, tryptophan, and thioflavin T analyses confirmed the establishment of a beta-sheet secondary structure as the curli conformations matured. Intermediate and mature curli fibrils were more immune stimulatory than early intermediate fibrils in vitro. The intermediate curli was cytotoxic to macrophages independent of Toll-like receptor 2. Mature curli fibrils had the highest DNA content and induced the highest levels of Isg15 expression and TNFα production in macrophages. In mice, mature curli fibrils induced the highest levels of anti-double-stranded DNA autoantibodies. The levels of autoantibodies were higher in autoimmune-prone NZBWxF/1 mice than wild-type C57BL/6 mice. Chronic exposure to all curli forms led to significant histopathological changes and synovial proliferation in the joints of autoimmune-prone mice; mature curli was the most detrimental. In conclusion, curli fibrils, generated during biofilm formation, cause pathogenic autoimmune responses that are stronger when curli complexes contain higher levels of DNA and in mice predisposed to autoimmunity. Public Library of Science 2022-08-16 /pmc/articles/PMC9380926/ /pubmed/35972973 http://dx.doi.org/10.1371/journal.ppat.1010742 Text en © 2022 Nicastro et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Nicastro, Lauren K.
de Anda, Jaime
Jain, Neha
Grando, Kaitlyn C. M.
Miller, Amanda L.
Bessho, Shingo
Gallucci, Stefania
Wong, Gerard C. L.
Tükel, Çagla
Assembly of ordered DNA-curli fibril complexes during Salmonella biofilm formation correlates with strengths of the type I interferon and autoimmune responses
title Assembly of ordered DNA-curli fibril complexes during Salmonella biofilm formation correlates with strengths of the type I interferon and autoimmune responses
title_full Assembly of ordered DNA-curli fibril complexes during Salmonella biofilm formation correlates with strengths of the type I interferon and autoimmune responses
title_fullStr Assembly of ordered DNA-curli fibril complexes during Salmonella biofilm formation correlates with strengths of the type I interferon and autoimmune responses
title_full_unstemmed Assembly of ordered DNA-curli fibril complexes during Salmonella biofilm formation correlates with strengths of the type I interferon and autoimmune responses
title_short Assembly of ordered DNA-curli fibril complexes during Salmonella biofilm formation correlates with strengths of the type I interferon and autoimmune responses
title_sort assembly of ordered dna-curli fibril complexes during salmonella biofilm formation correlates with strengths of the type i interferon and autoimmune responses
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9380926/
https://www.ncbi.nlm.nih.gov/pubmed/35972973
http://dx.doi.org/10.1371/journal.ppat.1010742
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