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E Pearlman, A Saint Andre, N Blackwell, JH Lass; A Critical Role For Endosymbiotic Wolbachia Bacteria And Tlr4 Signaling In The Pathogenesis Of Onchocerca Volvulus - Induced Corneal Inflammation (river Blindness) . Invest. Ophthalmol. Vis. Sci. 2002;43(13):946.
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Purpose: Endosymbiotic Wolbachia bacteria are abundant in parasitic filarial nematodes that infect over 200 million individuals worldwide, including Onchocerca volvulus, the parasite that causes river blindness. Using a murine model for river blindness, we examined the role of Wolbachia in development of corneal disease. Method: Three independent approaches were taken; firstly, we compared soluble extracts from Onchocerca volvulus worms from infected individuals treated with doxycycline (Wolbachia depleted). Secondly, we compared another species of filaria that naturally harbors Wolbachia (Brugia malayi) with a species that does not have Wolbachia (Acanthocheilonema viteae), Thirdly, we injected O. volvulus extracts containing Wolbachia into LPS hyporesponsive C3H/HeJ mice and compared responses with congenic, LPS responsive C3H/HeN mice. Development of stromal abnormalities was measured by Confocal Microscopy Throughput Focusing (CMTF), and neutrophil infiltration was determined by immunohistochemistry. Results: Neutrophil recruitment to the corneal stroma, and elevated stromal thickness and haze values by CMTF were significantly elevated in the extracts containing Wolbachia compared with extracts from either doxycycline treated worms or filarial species that do not have Wolbachia. Similarly, keratitis in C3H/HeN mice was significantly higher than in C3H/HeJ mice in the presence of Wolbachia. Conclusion: We demonstrate that it is not the nematode per se that causes the inflammation, but rather endotoxin-like products from endosymbiotic bacteria that mediate Tlr4 - dependent neutrophil infiltration to the cornea and play a dominant role in the development of stromal disease. These findings represent a significant change in our understanding of the pathogenesis of one of the most devastating effects of infection with filarial parasites.
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