Parasitic filarial nematodes infect over 200 million individuals worldwide, causing debilitating inflammatory diseases such as river blindness and lymphatic filariasis. Rickettsia - like Wolbachia bacteria are essential symbionts of the major pathogenic filarial nematode parasites of humans, including the Onchocerca volvulus, which causes river blindness. Using a murine model, we reported that Wolbachia play an essential role in the pathogenesis of Onchocerca keratitis, primarily by mediating neutrophil recruitment to the corneal stroma [Science 2002.295:1892]. In the current proposal, we will use microfilaria larvae (Mf) which harbor Wolbachia to examine the interaction between Wolbachia and the neutrophils that lead to stromal disease, focusing on mediators of neutrophil migration through the extracellular matrix (ECM) of the corneal stroma which include CXC chemokine receptors, beta 2 integrins, and matrix metalloproteinases. The experimental plan is a logical progression from studies conducted in the previous funding period, which focused on the role of vascular endothelial cells in recruitment of neutrophils from limbal vessels to the cornea. In addition to furthering our understanding of the role of Wolbachia in the pathogenesis of river blindness, results of proposed studies represent a novel approach to define the early molecular events underlying the interaction of neutrophils with ECM that lead to development of corneal haze. ? ?
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