Flag in the crossroads: flagellin modulates innate and adaptive immunity
Flag in the crossroads: flagellin modulates innate and adaptive immunity
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DOI：
10.1097/01.mog.0000194791.59337.28
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发表时间：
2006-01-01
影响因子：
2.5
通讯作者：
Gewirtz, AT
中科院分区：
文献类型：
--
作者：
Gewirtz, AT
综述的目的考虑到观察结果表明，细菌蛋白质鞭毛蛋白，鞭毛的主要结构成分，在介导肠道炎症与肠道病原体感染和炎症性肠病中起着重要作用。是激活先天免疫反应的主要手段，定义了活跃的肠道炎症。将血清学表达克隆的新技术应用于结肠炎小鼠模型发现，鞭毛蛋白也是在此类模型中驱动结肠炎的适应性免疫应答的主要靶标。人类研究观察到鞭毛蛋白也是与克罗恩病相关的免疫应答的主要抗原靶标。显性阴性Toll样受体5基因的携带者表现出对鞭毛蛋白的免疫的自然获得减少，表明对鞭毛蛋白的适应性免疫应答可能部分由Toll样受体5驱动。在某些遗传背景下，显性负性Toll样受体5与克罗恩病呈负相关，表明对鞭毛蛋白的免疫应答不仅与克罗恩病有关，而且可以促进致病应答。鞭毛蛋白也是克罗恩病相关的适应性免疫应答的优势抗原，因此将该分子置于作为肠道炎症标志的先天性和适应性免疫应答的十字路口。
Purpose of reviewTo consider observations suggesting that the bacterial protein flagellin, the primary structural component of flagella, plays a major role in mediating gut inflammation associated with infection by enteric pathogens and in inflammatory bowel disease.Recent findingsBiochemical dissection of an in-vitro model of bacterial-epithelial interactions revealed flagellin, via ligation of Toll-like receptor 5, to be a major means of activating the innate immune responses defining active intestinal inflammation. Application of the novel technique of serologic expression cloning to murine models of colitis discovered that flagellin is also a dominant target of the adaptive immune responses that drive colitis in such models. Human studies observed that flagellin was also a major antigenic target of immune responses associated with Crohn's disease. Carriers of dominant-negative Toll-like receptor 5 gene exhibit reduced natural acquisition of immunity to flagellin, indicating that the adaptive immune response to flagellin is likely driven, in part, by Toll-like receptor 5. In some genetic backgrounds dominant-negative Toll-like receptor 5 associated negatively with Crohn's disease, suggesting that immune responses to flagellin are not only associated with Crohn's disease, but can promote the pathogenic response.SummaryFlagellin is a major activator of innate immunity thus driving pathogen-induced acute inflammation and, perhaps, the active flares of inflammatory bowel disease. Flagellin is also a dominant antigen of the Crohn's disease-associated adaptive immune response, thus placing this molecule at the crossroads of the innate and adaptive immune responses that are the hallmark of intestinal inflammation.