BACKGROUND/OBJECTIVES A disruption of epithelial barrier function can lead to intestinal inflammation. Toll-like receptor (TLR) 2 activation by microbial products promotes intestinal epithelial integrity and overall gut health. Several bacterial species, including enteric bacteria, actively produce amyloid proteins as a part of their biofilms. Recognition of amyloid fibres found in enteric biofilms, termed curli, by the Toll-like receptor (TLR)2/1 complex reinforces barrier function. Here, we investigated the effect of purified curli fibres on inflammation in a mouse model of acute colitis. METHODS Bone marrow-derived macrophages as well as lamina propria cells were treated with curli fibres of both pathogenic Salmonella enterica serovar Typhimurium and commensal Escherichia coli Nissle 1917 biofilms. Mice were given 0.1 or 0.4 mg of purified curli orally 1 day post administration of 1% 2,4,6-trinitrobenzene sulphonic acid (TNBS) enema. Histopathological analysis was performed on distal colonic tissue taken 6 days post TNBS enema. RNA extracted from colonic tissue was subjected to RT-PCR. RESULTS Here we show that curli fibres of both pathogenic and commensal bacteria are recognised by TLR2 leading to the production of IL-10, immunomodulatory cytokine of intestinal homeostasis. Treatment of mice with a single dose of curli heightens transcript levels of Il10 in the colon and ameliorates the disease pathology in TNBS-induced colitis. Curli treatment is comparable to the treatment with anti-tumour necrosis factor alpha (anti-TNFα) antibodies, a treatment known to reduce the severity of acute colitis in humans and mice. CONCLUSION These results suggest that the bacterial amyloids had a role in helping to maintain immune homeostasis in the intestinal mucosa via the TLR2/IL-10 axis. Furthermore, bacterial amyloids may be a potential candidate therapeutic to treat intestinal inflammatory disorders owing to their remarkable immunomodulatory activity.

中文翻译：

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与生物膜相关的细菌淀粉样蛋白可减轻肠道炎症：使用卷曲纤维进行口服治疗可降低小鼠半抗原诱发的结肠炎的严重程度。

背景/目的上皮屏障功能的破坏可导致肠道炎症。微生物产物对Toll样受体（TLR）2的激活促进了肠上皮的完整性和整体肠道健康。包括肠道细菌在内的几种细菌会主动产生淀粉样蛋白作为其生物膜的一部分。Toll样受体（TLR）2/1复合物识别肠生物膜（称为curli）中发现的淀粉样蛋白纤维增强了屏障功能。在这里，我们调查了在急性结肠炎的小鼠模型中纯化的卷曲纤维对炎症的影响。方法用病原性肠炎沙门氏菌鼠伤寒沙门氏菌和共生大肠埃希氏大肠杆菌Nissle 1917生物膜的卷曲纤维处理骨髓来源的巨噬细胞和固有层细胞。给小鼠0.1或0。施用1％2,4,6-三硝基苯磺酸（TNBS）灌肠后1天口服4 mg纯化的卷曲。在TNBS灌肠后6天对远端结肠组织进行组织病理学分析。从结肠组织中提取的RNA经过RT-PCR。结果在这里我们显示，致病细菌和共生细菌的卷曲纤维都被TLR2识别，从而导致肠道稳态的免疫调节细胞因子IL-10的产生。用单剂量的卷心菜治疗小鼠可提高结肠中Il10的转录水平，并改善TNBS诱导的结肠炎的疾病病理。Curli治疗与抗肿瘤坏死因子α（抗TNFα）抗体的治疗相当，已知这种治疗可降低人和小鼠急性结肠炎的严重程度。结论这些结果表明，细菌淀粉样蛋白具有通过TLR2 / IL-10轴帮助维持肠粘膜免疫稳态的作用。此外，细菌淀粉样蛋白由于其显着的免疫调节活性，可能是治疗肠道炎性疾病的潜在候选疗法。