Pathogenesis of Fungal Keratitis

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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.