Helminthiasis

River blindness, a devastating tropical disease that affects 18,000,000 people in Africa, the Arabian peninsula, and Latin America, is caused by parasitic worms that burrow into the skin and release millions of tiny offspring that spread throughout the body. Moreover, the worms themselves probably are not the main culprits behind the disease, according to an international team of scientists. Instead, it is the worms' symbiotic cargo of Wolbachia bacteria that provokes the body's severe inflammatory response, leading to blindness and serious skin disorders.

River blindness is the second-leading infectious cause of blindness in the world. It is spread to humans by the bite of black flies infected with the parasitic worm Onchocerca volvulus. Its larvae, deposited by the fly's bite, burrow into the skin, where they mature and eventually send out tiny offspring called microfilariae that can migrate through the skin to the eye. When the microfilariae die, they trigger a severe immune response, causing eye inflammation and eventual vision loss.

Onchocerca don't travel alone on this journey. At all stages of their life cycle, the worms contain Wolbachia bacteria that appear to be essential companions. Research by Achim Hoerauf and Lars Volkmann of the Bernhard Nocht Institute for Tropical Medicine in Hamburg, Germany, suggests that the worms need Wolbachia to reproduce successfully.

With the close connection between worm and bacteria in mind, the researchers devised experiments to uncover Wolbachia's exact role in the development of river blindness. Using a mouse model for the disease, the researchers infected nine mice with extracts taken from worms treated with doxycycline (which contain relatively few Wolbachia) and with extracts from nontreated worms (with a normal Wolbachia load). Mice exposed to the treated extracts showed significantly less thickening and haze of the eye's cornea, and less signs of inflammation such as infiltration of white cells into the cornea, compared to mice infected with the untreated extracts. "These data show that Wolbachia itself has a major role in the pathology of the disease," indicates Eric Pearlman, associate professor of medicine and ophthalmology, Case Western Reserve University School of Medicine and University Hospitals of Cleveland (Ohio).

A body's innate immune response plays a large part in how the disease progresses. Mice lacking a key immune cell receptor molecule called TLR4 showed fewer signs of eye inflammation when exposed to Wolbachia-laden worm extract. These mice produced smaller amounts of other immune molecules and proteins that are normally recruited to fight infection, suggesting TLR4 might regulate Wolbachia-triggered inflammation by controlling the expression of these immune molecules.

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