NLRP3炎症小体识别犬小孢子菌感染的作用与机理研究

Microsporum canis (M.canis)is dermatophyte fungi,a species of genus Microsporun.Usually causes the skin and hair infection. M.canis is zoophilic fungi， frequenly resides in fur of cats and dogs。If human contact with these animal can transmitted to human and leads to tinea corporis and tinea capitis, affect the quality of people's lives. The number of skin disease caused by M.canis are increasing, because of the most people in city are keeping pets.Host recognition and response to invasion of pathogenic microorganisms highly dependents on the innate immune system. As an important component of innate immunity, the NLRP3 inflammasome has been proved to play an important role in response to infection from Candida albicans and other pathogenic fungi, therefore, NLRP3 may also be involved in the response to M.canis infection. The present project is designed to use a variety of cell and animal models that we have established to investigate the function and related mechanism of NLRP3 inflammasome function during M.canis infection. Our preliminary experiments have proved that NLRP3 is indeed involved in the innate immune response to M.canis, further mechanism studies are in progress. This project is expected to reveal the innate immune response to M.canis infection, and provide new molecular targets for the treatment of related diseases, which is of important theoretical and practical significance.

犬小孢子菌属于皮肤癣菌的小孢子菌属，是皮肤癣菌病的主要致病菌之一.常引起毛发和皮肤的感染。犬小孢子菌是亲动物性皮肤癣菌，常存在于猫、狗的皮毛上，人接触被感染的动物后传染人，引起体癣和头癣，影响人们的生活质量。随着城市中宠物饲养的迅速增加，犬小孢子菌引起的浅部真菌病日益增多。宿主对病原微生物的识别与应答高度依赖天然免疫系统。作为该系统的重要组分，NLRP3炎症小体在对白色念珠菌等病原真菌感染的应答中发挥非常重要的作用，因此NLRP3也可能参与对犬小孢子菌感染的应答。本项目准备运用我们已经建立的多种细胞和动物模型，研究NLRP3炎症小体在犬小孢子菌感染过程中的作用及相关机理。我们的初步实验已证明NLRP3确实参与了抗犬小孢子菌感染的天然免疫反应，进一步的机制研究正在进行中。本项目有望深入揭示犬小孢子菌致病的天然免疫反应机制，为皮肤癣菌病的治疗提供新的分子靶点，具有重要的理论和现实意义。

犬小孢子菌(M. canis)属于皮肤癣菌的小孢子菌属,是皮肤癣菌病的主要致病菌之一,常引起毛发和皮肤的感染,犬小孢子菌是亲动物性皮肤癣菌,常存在于猫、狗的皮毛上,人接触被感染的动物后传染人,引起体癣和头癣,影响人们的生活质量。随着城市中宠物饲养的迅速增加,犬小孢子菌引起的浅部真菌病日益增多。宿主对病原微生物的识别与应答高度依赖天然免疫系统。NLRP3炎性小体作为天然免疫的重要组分在机体免疫反应和疾病发生过程中具有重要作用。目前已知的炎症小体都可通过各自特异的途径将pro-Caspase-1活化为Caspase-1,进而诱发IL-1β和IL-18等炎症细胞因子的分泌。研究表明NLRP3炎症小体在对白色念珠菌等病原真菌感染的应答中发挥非常重要的作用,因此NLRP3也可能参与对犬小孢子菌感染的应答。本研究探讨NLRP3炎症小体在犬小孢子菌感染过程中的作用,揭示犬小孢子菌致病的天然免疫反应机制,为皮肤癣菌病的治疗提供新的分子靶点。本项目为了研究炎症小体是否参与宿主犬小孢子菌的感染,我们用分离于头癣患者的临床菌株去感染人单核细胞和小鼠的树突状细胞。用酶联免疫吸附法和蛋白免疫印迹法检测IL-1β的分泌和caspase-1的激活。结果：我们发现犬小孢子菌可引发人单核细胞和小鼠树突状细胞快速分泌IL-1β。这些数据表明,犬小孢子菌刺激免疫细胞产生IL-1β是依赖于体内的NLRP3炎症小体的作用。本项研究揭示了NLRP3炎性小体在宿主应对犬小孢子菌感染的先天免疫反应中的关键作用,犬小孢子菌引起的真菌感染可能通过炎症小体的激活引起炎症反应。