黄粉虫对细菌聚合型DAP-肽聚糖的模式识别及信号转导机制

发布时间：2018-03-23 12:01

本文选题：黄粉虫　切入点：聚合型DAP-PGN　出处：《沈阳药科大学》2011年博士论文

【摘要】：无脊椎动物的先天性免疫系统可以通过识别体液中的病原相关分子模式——PAMP,发现细菌或真菌的入侵。革兰阳性菌细胞壁中的Lys型肽聚糖(Lys-PGN)和真菌的β-1,3-葡聚糖(β-1,3-glucan)可以激活果蝇的Toll信号通路,革兰阴性菌和某些G+的二氨基庚二酸型肽聚糖(DAP-PGN)激活Imd信号通路。目前已有的研究多集中于胞内信号的传递及抗菌肽的产生机制,而对胞外信号的识别和传导,即对无脊椎动物如何利用有限肽聚糖识别受体(PRRs)识别病原菌的相关分子模式(PAMP),又是如何将胞外信号经过怎样的信号传递转变为胞内信号的过程了解还十分有限。课题组发现了在黄粉虫体内存在着一条三步蛋白水解信号通路,可以由Lys-PGN和β-1,3-glucan激活,并对Toll信号通路和黑色素合成通路进行调节。本文通过纯化另一种典型的PAMP——DAP-PGN及免疫相关蛋白及生物学性质研究,提出了DAP-PGN的胞外信号传递过程。聚合型DAP-PGN会与Tm-PGRP-SA形成复合物,经征集黄粉虫革兰阴性菌结合蛋白1(Tm-GNBP1),激活一条三步蛋白水解级联信号通路,进而切割Pro-Spatzle形成Spatzle, Spatzle作为Toll受体的配基分子,诱导抗菌肽——Tm-tenecin 2的合成。其过程与黄粉虫体内聚合型Lys-PGN诱导的信号通路相似。同时,发现了黄粉虫体内的一种新的肽聚糖识别受体(PGRP)家族成员——Tm-PGRP-SC2,核苷酸序列在GenBank的登陆号为AB560751.1,蛋白质接受号为BAJ23047.1。该蛋白存在于黄粉虫的血浆中,可被聚合型和单体型DAP-PGN诱导表达,经初步体外实验证明其生物学功能是一种对DAP-PGN有高效选择性的清除蛋白,可以负反馈调节聚合型和单体型DAP-PGN介导的免疫响应。以上结果表明黄粉虫幼虫可对入侵病原菌革兰阳性菌的Lys-PGN和革兰阴性菌及部分革兰阳性菌的DAP-PGN启动共同的免疫响应——Toll信号通路。同时,说明了黄粉虫幼虫与果蝇成虫之间对聚合型DAP-PGN识别具有不同的识别机制,也为昆虫先天性免疫响应的生物多样性提供了证据。
[Abstract]:The innate immune system of invertebrates can detect the invasion of bacteria or fungi by recognizing pathogen-associated molecular patterns in body fluids, pampp. The Lys type peptidoglycan (Lys-PGNN) in the cell wall of Gram-positive bacteria and 尾 -1n 3-glucanin of fungi can be detected. Activating the Toll signaling pathway in Drosophila, Gram-negative bacteria and some G diaminoheptate-type peptidoglycans (DAP-PGNs) activate the Imd signaling pathway. Recent studies have focused on intracellular signal transduction and the production of antimicrobial peptides, and on the recognition and transduction of extracellular signals. In other words, the understanding of how invertebrates use limited peptidoglycan recognition receptor (PRRs) to recognize pathogenic bacteria and how to transform extracellular signals into intracellular signals is still very limited. The team found that there is a three-step proteolytic signaling pathway in the body of powdery mildew, which can be activated by Lys-PGN and 尾 -1n 3-glucan. Toll signaling pathway and melanin synthesis pathway were regulated. By purifying another typical PAMP--DAP-PGN and immune-related proteins and their biological properties, the extracellular signal transduction process of DAP-PGN was proposed. Polymeric DAP-PGN forms complex with Tm-PGRP-SA. A three-step proteolytic cascade signal pathway was activated by collecting the Gram-negative bacterial binding protein (Tm-GNBP1) of powdery mildew, and then Pro-Spatzle was cut to form Spatzle.The Spatzle was used as the ligand molecule of Toll receptor. The synthesis of antimicrobial peptide Tm-tenecin 2 is similar to the signal pathway induced by polymeric Lys-PGN. A new peptidoglycan recognition receptor (PGRP) family member, Tm-PGRP-SC2, was found in Molitor's body. The nucleotide sequence in GenBank was AB560751.1, and the protein receptive number was BAJ23047.1. The protein was present in the plasma of Molitor Molitor and could be induced to express by polymeric and haplotype DAP-PGN. Its biological function was proved to be a highly selective scavenging protein for DAP-PGN in vitro. The immune response mediated by polymeric and haplotype DAP-PGN could be regulated by negative feedback. The above results showed that the larvae of powdery mildew could initiate a common immunity to the Lys-PGN of Gram-positive bacteria and the DAP-PGN of Gram-negative bacteria and some Gram-positive bacteria. Epidemic response Toll signaling pathway. At the same time, The results showed that there were different recognition mechanisms of polymeric DAP-PGN between the larvae and adults of Drosophila melanogaster, and it also provided evidence for the biodiversity of innate immune response of insects.
【学位授予单位】：沈阳药科大学
【学位级别】：博士
【学位授予年份】：2011
【分类号】：R392

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