Toll-Like Receptor 5 Stimulation Protects Mice from Acute Clostridium difficile Colitis
Toll-Like Receptor 5 Stimulation Protects Mice from Acute Clostridium difficile Colitis
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DOI：
10.1128/iai.01196-10
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发表时间：
2011-04-01
影响因子：
3.1
通讯作者：
Pamer, Eric G.
中科院分区：
文献类型：
--
作者：
Jarchum, Irene;Liu, Mingyu;Pamer, Eric G.
艰难梭菌是一种孢子形成细菌，感染人类的下肠道，是住院患者腹泻的最常见已知原因。艰难梭菌结肠炎是由毒素介导的，并在抗生素给药期间或之后发展。我们使用了C.艰难梭菌感染，它再现了人类疾病的主要特征，研究先天免疫激活对抵抗C。艰难感染我们发现，给予纯化的沙门氏菌衍生的鞭毛蛋白，一种Toll样受体5（TLR5）激动剂，可以保护小鼠免受C。通过延缓C.结肠和盲肠中艰难杆菌生长和毒素产生。TLR5刺激可显著改善C.艰难梭菌感染的小鼠，并减少上皮细胞损失。鞭毛蛋白治疗减少大肠上皮细胞凋亡，从而保护C.艰难感染我们证明，通过TLR刺激治疗的小鼠恢复肠道先天免疫状态，可改善肠道炎症并预防C。艰难梭菌结肠炎，可能提供一种方法，以防止C。艰难诱导的病理学。
Clostridium difficile is a spore-forming bacterium that infects the lower intestinal tract of humans and is the most common known cause of diarrhea among hospitalized patients. Clostridium difficile colitis is mediated by toxins and develops during or following antibiotic administration. We have used a murine model of C. difficile infection, which reproduces the major features of the human disease, to study the effect of innate immune activation on resistance to C. difficile infection. We found that administration of purified Salmonella-derived flagellin, a Toll-like receptor 5 (TLR5) agonist, protects mice from C. difficile colitis by delaying C. difficile growth and toxin production in the colon and cecum. TLR5 stimulation significantly improves pathological changes in the cecum and colon of C. difficile-infected mice and reduces epithelial cell loss. Flagellin treatment reduces epithelial apoptosis in the large intestine, thereby protecting the integrity of the intestinal epithelial barrier during C. difficile infection. We demonstrate that restoring intestinal innate immune tone by TLR stimulation in antibiotic-treated mice ameliorates intestinal inflammation and prevents death from C. difficile colitis, potentially providing an approach to prevent C. difficile-induced pathology.