Filarial nematodes cause some of the most debilitating diseases in tropical medicine. Recent studies, however, have implicated the parasites' endosymbiotic Wolbachia bacteria, rather than the nematode, as the cause of inflammatory-mediated filarial disease. Soluble extracts of a variety of filarial species stimulate
innate inflammatory responses, which are absent or reduced when using extracts derived from species either devoid of bacteria, or those cleared of bacteria by
antibiotics. Characterization of the molecular nature of the bacterial derived inflammatory stimulus points toward an
endotoxin-like activity that is dependent on the
pattern recognition receptors CD14 and TLR4 and can be inhibited by
lipid A antagonists. TLR4 dependent
inflammation has been shown to occur in the systemic inflammatory adverse reaction to Brugia malayi following anti-filarial
chemotherapy and in the development of neutrophil-mediated ocular
inflammation in a mouse model of
river blindness. The development of acute and severe inflammatory responses in people infected with Brugia malayi and Onchocerca volvulus is associated with the release of Wolbachia into the blood following death or damage of the worms after anti-filarial
chemotherapy. Together these studies suggest that Wolbachia are the principal cause of acute inflammatory filarial disease. Accumulated exposure to acute episodes of
inflammation may also underlie the development of chronic filarial pathology. The use of
antibiotic therapy to target Wolbachia of filarial parasites may therefore provide a means to prevent the development of filarial pathology.