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【目的】大量的证据表明机体正常的免疫活动在很大程度上依赖于免疫系统和肠道菌群的相互作用,具体表现为免疫系统对病原菌进行免疫清除而对益生菌耐受。其中,免疫系统的Toll样受体(Toll-like receptors,TLRs)和来自肠道菌群的微生物相关的分子模型(Microorganism associated molecular patterns,MAMPs)被认为在宿主免疫系统对病原菌和益生菌的区分中发挥了重要作用,因为TLRs对MAMPs的识别能够激活先天性和获得性免疫反应。在TLRs对MAMPs的识别中,只有TLR5对细菌鞭毛蛋白的识别是基于蛋白-蛋白的相互作用,比较容易对其结合方式进行研究。因此,我们研究的主要目的就是要确定TLR5与鞭毛蛋白的相互作用是如何影响宿主区分病原菌和益生菌的。【方法】构建了多种肠道细菌(包括益生菌和病原菌)鞭毛蛋白的系统发育树,并比对了鞭毛蛋白的TLR5识别序列。【结果】发现病原菌和益生菌的鞭毛蛋白序列有所不同,尤其是TLR5结合并识别的鞭毛蛋白位点。【结论】病原菌和益生菌不同的鞭毛蛋白识别区域可能是鞭毛细菌适应TLR5识别下生存的结果,据此宿主能够对病原菌和益生菌进行区分。此外,相关研究表明TLRs在肠上皮细胞的分布具有基底侧和顶端的两极性,能够分别引发对病原菌的免疫反应和对益生菌的免疫耐受,从而抵御病原菌的入侵感染、与益生菌和平共处。鞭毛蛋白和TLR5蛋白的相互作用反映了肠道菌群和免疫系统在分子层面的相互作用和共同进化,是宿主区分病原菌和益生菌的分子机制之一。
【Objective】 There is a lot of evidence that the normal immune activity of the body depends largely on the interaction between the immune system and the intestinal microflora. The specific manifestation is that the immune system can tolerate the probiotics by immunizing the pathogenic bacteria. Among them, immune system Toll-like receptors (TLRs) and microorganism associated molecular patterns (MAMPs) from the gut microbiota are thought to distinguish between pathogenic bacteria and probiotics in the host immune system Has played an important role because TLRs recognize MAMPs that activate innate and adaptive immune responses. Among TLRs’ recognition of MAMPs, only recognition of bacterial flagellin by TLR5 is based on the protein-protein interaction, and it is relatively easy to study its binding mode. Therefore, the main purpose of our study is to determine how the interaction of TLR5 with flagellin affects the host’s differentiation of pathogens and probiotics. 【Method】 The phylogenetic tree of many kinds of intestinal bacteria (including probiotics and pathogens) flagellin was constructed and compared with the TLR5 recognition sequence of flagellin. 【Results】 The flagellin sequences of pathogen and probiotic bacteria were found to be different, especially the flagellin site that TLR5 binds to and recognizes. [Conclusion] The different flagellin recognition regions of pathogenic bacteria and probiotics may be the result of flagellate bacteria adapted to survival under the TLR5 recognition, whereby the host can distinguish the pathogenic bacteria from the probiotics. In addition, relevant studies have shown that the distribution of TLRs in the gut epithelium has basal and apical bipolarities that can elicit an immune response to the pathogenic bacteria and immune tolerance to the probiotics, respectively, thereby preventing invasion by pathogenic bacteria and peaceful coexistence with probiotics . The interaction of flagellin and TLR5 protein reflects molecular interactions and coevolution at the molecular level between the gut flora and the immune system and is one of the molecular mechanisms by which hosts distinguish pathogens and probiotics.