皮肤癣菌是临床最常见的丝状真菌，其感染在全球的发病率高达20-25%。须癣毛癣菌复合体作为常见的皮肤癣菌，其致病菌种趾间毛癣菌、须癣毛癣菌、断发毛癣菌和马毛癣菌所致的感染临床表现不同，可造成皮肤、皮下甚至侵袭性感染。这些菌种在致病力方面存在的差异和关键致病分子及其差异机制均不明确。本课题组在前期工作明确了我国临床分离的须癣毛癣菌复合体中三个菌种的致病及分子分类特征基础上，拟利用本实验室成熟的真菌感染与宿主免疫研究平台，从探讨其利用角蛋白能力、产生角蛋白酶活性的能力差异及其引发的宿主免疫应答和免疫逃逸出发，通过体外实验和动物实验，采用3D皮肤模型和小动物活体成像技术，结合比较基因组和互作转录组学，探究须癣毛癣菌复合体内不同菌种致病力的差异及相关的重要分子，试图阐明导致菌种间致病力差异的机制。本研究不仅对了解须癣毛癣菌复合体致病力差异机制具有重要意义，还为寻找新的抗真菌药物作用靶点提供依据。

Dermatophytes are the most common filamentous fungi in clinic, which cause human infections with a worldwide prevalence rate as high as 20-25%. As one of the most common dermatophytes, Trichophyton mentagrophytes complex contains species causing quite different clinical manifestations, such as T. interdigitale, T. mentagrophytes, T. tonsurans and T. equinum. They are responsible for cutaneous, subcutaneous, and even invasive infections. The exact differences of pathogenicity among these species, its mechanism, and the key pathogenic molecules involved still need further investigations. In our previous work, we have identified the pathogenic characteristics and molecular classification of these three species in the Trichophyton mentagrophytes complex in China, and established full-fledged platform to study host-fungus interactions. This proposed study will first explore the differences in keratin utilization and keratinase activity among these strains, and further discover their host immune responses and their immune escape mechanisms, using in vitro experiments and animal models, especially 3D human epidermal equivalents and opticalin vivo imaging. Moreover, we plan to utilize comparative genomics and Dual RNA-seq techniques, to explore the important molecules responsible for the difference in pathogenicity among different species in the complex, in order to explain its mechanisms. Our proposed study may build a better understanding of the variation of pathogenicity and the mechanisms in this complex, and provide an important theoretical basis to search for novel antifungal targets and treatment strategies in the future.