Filariasis Research Laboratory, Division of Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK
Address for correspondence: Mark J. Taylor, Filariasis Research Laboratory, Division of Molecular and Biochemical Parasitology, Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK. Voice: + 44 151 708 9393; fax: + 44 151 705 3371.
mark.taylor{at}liverpool.ac.uk
Ann. N.Y. Acad. Sci. 990: 444-449 (2003).
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.
