Role of γδT cells in skin homeostasis and protective immunity during experimental dermatophytosis

γδT 细胞在实验性皮肤癣菌病期间皮肤稳态和保护性免疫中的作用

• 批准号: 431861465
• 负责人: Professor Dr. Immo Prinz
• 金额: --
• 依托单位: Consejo Nacional de Investigaciones Científicas y Técnicas
• 依托单位国家: 德国
• 项目类别: Research Grants
• 资助国家: 德国
• 项目状态: 未结题
• 来源: https://gepris.dfg.de/gepris/projekt/431861465?language=en
• 关键词: Role; cells; skin; homeostasis; protective

Human fungal diseases continue to represent a major global health problem, in particular in children, in the elderly and in immune-deficient individuals. In recent decades, our understanding of the molecular pathways that control innate recognition of fungi and antifungal responses elicited by myeloid cells has significantly improved. However, we still understand less about organ-specific adaptive immune responses and cytokine networks that control fungal growth. Dermatophytoses are skin infections caused by keratinophilic filamentous fungi affecting approximately 25% of the world population, thereby representing the fourth most prevalent cause of human disease. Despite this enormous incidence, disease pathogenesis and host responses to dermatophytes are scarcely investigated in comparison to other fungal infections. Here, the Argentinean and German partners will jointly investigate the skin’s immune responses to dermatophytosis and address how commensal bacteria and pathogenic fungi drive skin immune homeostasis. Innate γδT lymphocytes are emerging as central players in skin immunity against pathogens as well as in maintaining homeostasis with commensal microorganisms. Therefore, we will monitor their antifungal functions against dermatophytes in an experimental model of epicutaneous infection with Microsporum spp., which mimics human dermatomycosis. Specifically, we will investigate the role of dermal γδT cells that produce the pro-inflammatory cytokine interleukin-17-producing in response to dermatophyte infection. Furthermore, we will study the microbial and metabolic factors that modulate immune homeostasis between interleukin-17-producing immune cells and pathogenic or commensal fungi of the skin. This proposal outlines a highly collaborative and complementary research project that will mutually benefit the laboratories of Dr. Laura Chiapello (CIBICI-CONICET) and Dr. Immo Prinz (Institute of Immunology, Hannover, Germany). The Argentine group provides experience in the management of pathogenic fungi and experimental infections, and the German group is experienced in γδT cell biology and the in vivo study of immune cell dynamics in tissues.

人类真菌疾病仍然是一个主要的全球健康问题，特别是在儿童、老年人和免疫缺陷个体中。近几十年来，我们对控制真菌先天识别和骨髓细胞引起的抗真菌反应的分子途径的理解有了显着提高。然而，我们仍然对器官特异性适应性免疫反应和控制真菌生长的细胞因子网络了解较少。皮肤癣菌病是由嗜角质丝状真菌引起的皮肤感染，影响约25%的世界人口，从而代表人类疾病的第四大流行原因。尽管这种巨大的发病率，疾病的发病机制和宿主对皮肤癣菌的反应很少调查相比，其他真菌感染。在这里，阿根廷和德国合作伙伴将联合研究皮肤对皮肤真菌病的免疫反应，并解决共生细菌和致病真菌如何驱动皮肤免疫稳态的问题。先天性γδT淋巴细胞正在成为皮肤对病原体的免疫以及维持体内微生物稳态的核心参与者。因此，我们将在小孢子菌属表皮感染的实验模型中监测它们对皮肤真菌的抗真菌功能，类似于人类皮肤真菌病具体来说，我们将研究皮肤γδT细胞的作用，这些细胞产生促炎细胞因子白细胞介素-17，以响应皮肤真菌感染。此外，我们将研究调节产生白细胞介素-17的免疫细胞与皮肤病原性或共生真菌之间免疫稳态的微生物和代谢因素。该提案概述了一个高度合作和互补的研究项目，该项目将使Laura Chiapello博士（CIBICI-CONICET）和Immo Prinz博士（免疫学研究所，汉诺威，德国）的实验室互惠互利。阿根廷小组提供了病原真菌和实验感染管理方面的经验，德国小组在γδT细胞生物学和组织中免疫细胞动力学的体内研究方面经验丰富。