筛选和鉴定许兰毛癣菌中激活NLRP3炎症小体的温度调控因子及其激活机制的研究

许兰毛癣菌导致的黄癣是头癣最严重的临床类型，南疆儿童头癣高流行的原因值得关注。前期研究发现许兰毛癣菌（活菌）能激活NLRP3炎症小体，被视为是许兰毛癣菌感染控制中一个重要因素，而热灭活后的许兰毛癣菌（死菌）虽然不能生长但仍能激活NLRP3炎症小体而具有致病性，我们推测在该菌中存在对热敏感的组份（温度调控因子）影响NLRP3炎症小体的激活和某些信号通路的调节，参与毒力形成。本研究采用转录组测序的方法，筛选和鉴定该菌中的温度调控因子，利用基因敲入，在细胞水平测试这些靶标基因对NLRP3炎症小体的激活。若有激活，进一步的利用基因敲除靶基因，构建许兰毛癣菌突变株，通过测试剂量依赖性，生理化学刺激，炎症小体基因敲除细胞系，炎症小体小鼠模型等体内外实验，深入研究许兰毛癣菌的温度调控因子激活NLRP3炎症小体和调控机制。该研究对深入理解宿主识别与清除该菌感染的机制非常重要，为头癣防治新策提供依据。

Tinea favosa is the most serious clinical type of tinea capitis caused by Trichophyton schoenleinii(T.schoenleinii),The children of tinea capitis,in the south of Xinjiang high prevalence should be concerned.Our previous study found T.schoenleinii(living strain) can activate the NLRP3 inflammasome, therefore, it is considered to be an important factor in the control of T.schoenleinii infection.However, the heat-killed T.schoenleinii(dead strain) though not able to grow, but it still can activate NLRP3 inflammasome and has pathogenicity. So we hypothesized that the presence of heat sensitive components in T.schoenleinii affected the activation of NLRP3 inflammasome and the regulation of certain signaling pathways.So the transcriptome sequencing technologies was employed to screening and identification some of the temperature regulating factors of the T.schoenleinii, then will use Knock in technique to test target gene activated NLRP3 inflammasome at the cellular level.If activated, further, will knockout the target genes to the construction of mutant strai 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 the temperature regulating factor of T.schoenleinii infection. The study on understanding the inflammasome recognition and removal mechanism of the T.schoenleinii infection is very important, aslo for the development of new strategy of prevention and treatment of tinea capitis provide important theoretical basis.