Pathogenesis of Fungal Keratitis

描述（申请人提供）：致病性镰刀菌和曲霉菌是美国和世界范围内视力丧失的重要原因。拟议的研究将集中于IL-17产生多形核白细胞（PMN-17）通过促进活性氧的产生、真菌杀死和角膜混浊在真菌性角膜炎中的作用。初步数据表明，这些以前未表征的细胞在真菌感染的早期反应中起重要作用，并且存在于受感染个体的角膜中。目的1将检查c型凝集素在巨噬细胞和树突状细胞对这些病原体的反应中产生IL-6和IL-23的作用。Aim 2将检测IL-17受体介导的角膜趋化因子产生导致PMN-17细胞募集，Aim 3将检测IL-17诱导的NADPH氧化酶和PMN-17细胞介导的犬尿氨酸ROS产生。这些研究结果将进一步加深我们对PMN-17细胞在真菌性角膜炎中的作用的理解，并确定抗炎干预以限制角膜组织损伤的新靶点。

DESCRIPTION (provided by applicant): Pathogenic Fusarium and Aspergillus molds are an important cause of vision loss in the USA and worldwide. Proposed studies will focus on the role of IL-17 producing polymorphonuclear leukocytes (PMN-17) in fungal keratitis by promoting reactive oxygen species production, fungal killing and corneal opacification. Preliminary data show that these previously uncharacterized cells have an important role in the early response to fungal infection, and are present in the corneas of infected individuals. Aim 1 will examine the role of c-type lectins in IL-6 and IL-23 production by macrophages and dendritic cells in response to these pathogens. Aim 2 will examine IL-17 receptor mediated chemokine production in the cornea leading to recruitment of PMN-17 cells, and Aim 3 will examine IL-17 induced NADPH oxidase and kynurenine mediated ROS production by PMN-17 cells. Results of these studies will further our understanding of the role of PMN-17 cells in fungal keratitis and identify novel targets for anti-inflammatory intervention to limit tissue damage in the cornea.