The role of bacterial cell wall dimers in the innate immune response (970.1)
The role of bacterial cell wall dimers in the innate immune response (970.1)
复制标题
细菌细胞壁二聚体在先天免疫反应中的作用 (970.1)
DOI：
10.1096/fasebj.28.1_supplement.970.1
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
C. Grimes
中科院分区：
文献类型：
--
作者：
Lauren A. Genova;James E. Melnyk;Vishnu Mohanan;C. Grimes
先天免疫系统是人体抵御病原体的第一道防线。先天免疫系统是由病原体相关分子模式(PAMPs)触发的，这些模式识别受体(PRRs)如Toll样受体(TLRs)和Nod样受体(NLRs)。这项研究项目的重点是更好地了解先天免疫系统如何感知和应对细菌的存在。具体地说，我们的团队感兴趣的是核苷酸结合寡聚化结构域包含蛋白2(NOD2)和胞浆二肽(MDP)之间的关系，NOD2是一种发现在哺乳动物宿主细胞胞浆中的NLR蛋白，MDP是已知的可引起免疫反应的最小细菌细胞壁片段。当NOD2突变时，信号通路被扰乱，出现无法控制的炎症，导致慢性炎症性肠道疾病，如克罗恩病。为了发现如何更好地治疗这些疾病，必须更多地了解NOD2和MDP是如何相互作用的，这一机制目前尚不清楚。格里姆斯实验室此前已经证明，NOD2在体外与MDP结合；然而，研究表明，如果使用包含多个MDP的分子，可能会在宿主中引发更高的免疫反应，这表明多价作用正在发挥作用。这个项目突出了我目前的研究进展，即合成各种新型的MDP二聚体，以测试NOD2和MDP之间的多价相互作用。
The innate immune system is the body’s first line of defense against pathogens. The innate immune system is triggered by pathogen associated molecular patterns (PAMPs) that are recognized by pattern recognition receptors (PRRs) such as Toll‐like receptors (TLRs) and Nod‐like receptors (NLRs). This research project focuses on providing a better understanding of how the innate immune system senses and responds to the presence of bacteria. Specifically, our group is interested in the relationship between Nucleotide‐binding oligomerization domain‐containing protein 2 (Nod2), an NLR protein found in the cytosol of mammalian host cells, and muramyl dipeptide (MDP), the smallest bacterial cell wall fragment known to elicit an immunological response. When Nod2 is mutated, the signaling pathway becomes disrupted and uncontrollable inflammation arises, leading to chronic inflammatory bowel disorders such as Crohn’s disease. In order to discover how to better treat these diseases, it is imperative to learn more about how Nod2 and MDP interact, a mechanism which is currently unknown. The Grimes Lab has previously shown that Nod2 binds to MDP in vitro; however, research suggests that a heightened immunological response may be elicited in a host if molecules containing multiple MDP’s are used, suggesting multivalency is at play. This project highlights my current research progress to synthesize a variety of novel MDP dimers to test for a multivalent interaction between Nod2 and MDP.