Bacterial amyloid curli acts as a carrier for DNA to elicit an autoimmune response via TLR2 and TLR9
| العنوان: | Bacterial amyloid curli acts as a carrier for DNA to elicit an autoimmune response via TLR2 and TLR9 |
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| المؤلفون: | Sarah Tursi, Ernest Lee, Michael Lee, Nicole Mederios, Paul Wilson, Stefania Gallucci, Gerard C Wong, Cagla Tukel |
| المصدر: | The Journal of Immunology. 198:77.12-77.12 |
| بيانات النشر: | The American Association of Immunologists, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Immunology, Immunology and Allergy |
| الوصف: | Bacterial biofilms are associated with numerous human infections. The predominant protein expressed in enteric biofilms is amyloid curli which forms immunogenic complexes with DNA. Infection with curli-expressing bacteria or systemic exposure to purified curli-DNA complexes triggers autoimmunity via the generation type I interferons (IFNs) and anti-double stranded (ds) DNA autoantibodies. DNA complexed with curli stimulates Toll-like receptor (TLR) 9 through a two-step mechanism. First, the cross beta-sheet structure of curli is bound by cell-surface TLR2, enabling internalization of the complex into endosomes. After internalization, the curli-DNA immune complex binds strongly to TLR9, inducing production of type I IFNs. Upon stimulation of macrophages with curli-DNA complexes, only 5% of TLR2−/− macrophages harbored intracellular curli, suggesting that TLR2 drives the internalization of curli-DNA complexes. Suppression of TLR2 internalization led to a significant decrease in Ifnβ expression. Structural analysis using small-angle X-ray scattering revealed that incorporation of DNA into curli fibrils results in the formation of ordered curli-DNA immune complexes resulting in optimal spacing to TLR9. Production of anti-dsDNA autoantibodies and type I IFNS in response to curli-DNA fibers was attenuated in the TLR2−/−, TLR9 mutant, and TLR2−/− - TLR9 mutant mice compared to wildtype mice, suggesting that TLR2 and TLR9 are critical for the autoimmune immune response. Overall, our results identify a pivotal series of events that leads to the severe pro-autoimmune effects of amyloid-expressing bacteria. |
| تدمد: | 1550-6606 0022-1767 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::273f61c4dbdc317cc49bd8d437c2ce8c https://doi.org/10.4049/jimmunol.198.supp.77.12 |
| رقم الأكسشن: | edsair.doi...........273f61c4dbdc317cc49bd8d437c2ce8c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15506606 00221767 |
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