群体感应信号分子对免疫系统的影响  

Effects of Quorum Sensing Molecules on The Immune System

作　　者：马文敏 陈轩岐 马红霞 张文慧[1] 孔令聪[2] 周昱伽 胡元元 贾宇 MA Wen-Min;CHEN Xuan-Qi;MA Hong-Xia;ZHANG Wen-Hui;KONG Ling-Cong;ZHOU Yu-Jia;HU Yuan-Yuan;JIA Yu(College of Life Sciences,Jilin Agricultural University,Changchun 130118,China;College of Veterinary Medicine,Jilin Agricultural University,Changchun 130118,China;Engineering Research Center of Bioreactor and Pharmaceutical Development,Ministry of Education,Jilin Agricultural University,Changchun 130118,China;Zhejiang Keming Biopharmaceutical Co.,LTD,Shaoxing 312500,China)

机构地区：[1]吉林农业大学生命科学学院,长春130118 [2]吉林农业大学动物医学院,长春130118 [3]吉林农业大学生物反应器与药物开发教育部工程研究中心,长春130118 [4]浙江可明生物医药有限公司,绍兴312500

出　　处：《生物化学与生物物理进展》2024年第11期2853-2867,共15页Progress In Biochemistry and Biophysics

基　　金：吉林省自然科学基金(20230101199JC)资助项目。

摘　　要：近年来,宿主导向的抗菌药物研发逐步成为抗感染领域的热点。通过研究宿主和病原菌的相互作用机制,发现免疫系统是宿主导向抗菌药物的关键靶点之一。在以细菌为首的微生物种群中存在一种通讯交流系统,称为群体感应系统,其主要用于调整多微生物群落结构并协调群体行为。当微生物分泌的群体感应信号分子达到阈值浓度时,激活了群体感应系统并引起微生物整体基因表达变化。除了对微生物自身密度的调控外,群体感应信号分子还可以作为病原微生物与宿主之间的纽带进入宿主免疫系统并发挥作用,在影响免疫细胞形态结构、细胞因子分泌以及诱导细胞凋亡等方面导致宿主免疫损伤,造成宿主免疫功能失常。因此以宿主免疫系统为作用靶点,以群体感应信号分子为目标开发抗菌药物,可以有效抑制病原菌对宿主免疫功能的侵袭并协助宿主抗菌。本文对重要群体感应信号分子引发的宿主免疫应答反应机制进行综述,深入探究宿主导向抗菌药物的可能作用靶点,以期为预防或治疗病原体感染以及相关药物研发提供新方向。In recent years,the development of host-acting antibacterial compounds has gradually become a hotspot in the field of anti-infection.Through research on the interaction mechanism between hosts and pathogenic bacteria,it has been found that the immune system is one of the key targets of host-acting antibacterial compounds.There is a communication system called the quorum sensing system in microorganisms,which mainly adjusts the structure of multi-microbial community and coordinates the group behavior.When the quorum sensing molecules secreted by microorganisms reach a threshold concentration,the quorum sensing system is activated and the overall gene expression of the microorganism is changed.In addition to regulating the density of microorganisms,quorum sensing molecules can also act as a link between pathogenic microorganisms and hosts,entering the host immune system and playing a role in affecting the morphological structure of immune cells,secreting cytokines,and inducing apoptosis,leading to host immune injury and causing host immune dysfunction.The key mechanism of 3-oxo-C12-HSL and other acyl-homoserine lactone(AHL)molecules in the innate immune system has been extensively studied.The lipid solubility allows AHLs to pass through the plasma membrane of host immune cells easily and induce dissolution of lipid domains.Then,it acts through signaling pathways such as p38MAPK and JAK-STAT,further influencing the immune cell’s defense response to bacteria and potentially leading to cell apoptosis.Additionally,the human lactonase paraoxonase 2,which can degrade 3-oxo-C12-HSL,has been found in macrophage.It acts as an immune regulator that promotes macrophage phagocytosis of pathogens and is hypothesized to have the ability to reduce bacterial resistance.The mechanism of quorum sensing molecules in the adaptive immune system is less studied,the current results suggest that 3-oxo-C12-HSL is closely related to the mitochondrial pathway in host immune cells.For example,3-oxo-C12-HSL induces apoptosis of Jurkat cells

关 键 词：群体感应系统 群体感应信号分子 免疫应答 免疫细胞 

分 类 号：Q7[生物学—分子生物学] Q93[医药卫生—免疫学] R392.1[医药卫生—基础医学]