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Are Bacterial "Hitchhikers" the True Cause of River Blindness?

Wolbachia bacteria, symbionts of the nematode long blamed for river blindness, may be the true culprits behind this syndrome.

Infection with the filarial nematode Onchocerca volvulus causes river blindness. Dying microfilaria that have traveled to the eye induce an inflammatory response that leads to irreversible eye damage. Wolbachia bacteria are essential symbionts of these nematodes, required for nematode embryogenesis. New animal-model data suggest that Wolbachia, not O. volvulus, may be the primary initiator of the eye-damaging inflammation.

Doxycyline treatment of O. volvulus largely eliminates coexistent Wolbachia. When injected into the corneal stroma of mice, extracts from doxycycline-treated O. volvulus worms induced significantly less stromal inflammation than extracts from untreated worms did. Toll-like receptor 4 (TLR4) on host cells is critical in mediating inflammatory responses to bacterial lipopolysaccharide (LPS). Wolbachia-containing O. volvulus extracts -- injected into the corneas of a mouse strain (C3H/HeJ) known to respond suboptimally to LPS because of a genetic defect in Tlr4 -- caused less inflammation than in a mouse strain (C3H/HeN) that expresses normal TLR4. Expression of corneal proinflammatory receptors and of LPS-upregulated products that contribute to neutrophil recruitment was also lower in the TLR4-defective mice. No difference was observed between strains in eosinophil recruitment.

Comment: These data support the possibility that Wolbachia components (for example, LPS) released from dying O. volvulus microfilaria, not components of the nematode itself, may be largely responsible for the intense immune response that leads to river blindness. A limitation of the study is that it used extracts of the O. volvulus worms and not of the microfilaria that are present in the human eye. Nevertheless, if these observations can be extended to human disease, antibiotics that eliminate Wolbachia could potentially decrease O. volvulus-related blindness.

— Bradley E. Britigan, MD

Published in Journal Watch Infectious Diseases April 11, 2002

Citation(s):

Saint André A et al. The role of endosymbiotic Wolbachia bacteria in the pathognesis of river blindness. Science 2002 Mar 8; 295:1892-5.

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Pennisi E. New culprit emerges in river blindness. Science 2002 Mar 8; 295:1809-11.

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