The role of endosymbiotic Wolbachia bacteria in the pathogenesis of river blindness. Andre AS, Blackwell NM, Hall LR, Hoerauf A, Bratting NW, Volkmann L, Taylor MJ, Ford L, Hise AG, Lass JH, Diaconu E, Pearlman E. Science 2002;295:1892–1895.

Abstract

Wolbachia bacteria are essential symbionts of the major pathogenic filarial nematode parasites. The authors sought to determine the role of Wolbachia in the pathogenesis of ocular onchocerciasis. Soluble extracts of doxycycline-treated and untreated O. volvulus were injected into murine corneas. Extracts for doxycycline-treated worms induced significantly lower stromal thickness, stromal haze, and neutrophil infiltration than extracts from untreated worms. Since TLR4 is essential for host cell response, the authors determined if Wolbachia mediates corneal pathology by activating TLR4. O. volvulus extracts containing Wolbachia were injected into corneas of C3H/HeJ mice which are hypersensitive to LPS owing to a single point mutation in the T14, and immune responses to these extracts were compared from cogenic, LPS-responsive C3H/HeN mice. Stromal thickness, stromal haze, and neutrophil recruitment were significantly diminished in C3H/HeJ mice, indicating that TLR4 regulates the development of O. volvulus keratitis. Further experiments indicated that, in contrast to neutrophils, eosinophil recruitment to the corneal stromas is not regulated by TLR4. Taken together, these findings demonstrate an essential role for Wolbachia and TLR4 in the corneal pathology of river blindness caused by O. volvulus. In infected individuals, the innate inflammatory response is likely to be initiated by release of Wolbachia endotoxin-like molecules from dead and degenerating O. volvulus. This study indicates that clearance of Wolbachia by antibiotic treatment may reduce and prevent ocular onchocerciasis.—Hans E. Grossniklaus