Role of MKP1 in fungal disease.

MKP1 在真菌病中的作用。

• 批准号: 2606318
• 金额: --
• 依托单位: King's College London
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2606318
• 关键词: Role; MKP1; fungal; disease.

The fungal pathogen Candida albicans, the causative agent of thrush, causes millions of infections annually in people worldwide. The search for an explanation for how this fungus causes disease and immune activation has remained at the forefront of medical mycology and immunology. In recent years, we have identified a key signalling mechanism involving the phosphatase MKP1, which enables epithelial tissues to discriminate between the commensal (yeast) and pathogenic (hyphal) states of C. albicans [1]. This discriminatory mechanism is based on the host recognition of candidalysin, a cytolytic peptide toxin secreted by the fungus, and which is encoded by its parent gene ECE1 [2]. Candidalysin is produced by the hyphal form of C. albicans and is encoded by its parent gene ECE1. Ece1p is processed in the fungus to generate candidalysin, which is then secreted [3]. Candidalysin acts as a cytolytic toxin and activates host cells by inducing pores in the cell membrane. This results in the activation of a key signalling pathway involving MKP1, which is required for cytokine induction and neutrophil recruitment [4]. The phosphatase MKP1 is activated via the EGFR-ERK1/2 pathway but regulates the p38 pathway, another pathway activated by candidalysin. Importantly, candidalysin is the only damage inducing factor that C. albicans possesses. MKP1 is a phosphatase that regulates host responses via the MAPK (mitogen-activated protein kinase) pathway. In vitro, MKP1 is activated via surface receptors and cell damage caused during infection. Currently, the role of MKP1 during fungal disease is unknown.

真菌病原体白色念珠菌是鹅口疮的病原体，每年在全世界引起数百万人感染。寻找这种真菌如何引起疾病和免疫激活的解释一直是医学真菌学和免疫学的前沿。近年来，我们已经确定了一个关键的信号机制，涉及磷酸酶MKP 1，这使得上皮组织之间的区别的寄生（酵母）和致病（菌丝）状态的C。白色念珠菌[1]。这种区分机制是基于宿主对念珠菌溶素的识别，念珠菌溶素是一种由真菌分泌的溶细胞肽毒素，由其亲本基因ECE 1编码[2]。 放线菌素是由C.白念珠菌，由其亲本基因ECE 1编码。Ece 1 p在真菌中加工产生念珠菌溶素，然后分泌[3]。溶藻素作为一种细胞溶解毒素，通过在细胞膜上诱导孔来激活宿主细胞。这导致涉及MKP 1的关键信号传导途径的激活，这是细胞因子诱导和中性粒细胞募集所需的[4]。磷酸酶MKP 1通过EGFR-ERK 1/2途径激活，但调节p38途径，另一种途径由念珠菌溶解素激活。重要的是，念珠菌溶素是唯一的损伤诱导因子，C。白色念珠菌拥有。MKP 1是一种磷酸酶，通过MAPK（丝裂原活化蛋白激酶）途径调节宿主反应。在体外，MKP 1通过表面受体和感染期间引起的细胞损伤被激活。目前，MKP 1在真菌疾病中的作用尚不清楚。