Toll-like receptor 4 (TLR4) has been shown to be important for the induction of Th2-dependent immune responses in mice. Protective immunity against larval Onchocerca volvulus in mice depends on the development of a Th2 immune response mediated by both interleukin-4 (IL-4) and IL-5. In addition, O. volvulus contains the rickettsial endosymbiont Wolbachia, which has molecules with lipopolysaccharide-like activities that also signal through TLR4. We therefore hypothesized that protective immunity to O. volvulus would not develop in C3H/HeJ mice which have a mutation in the Tlr4 gene (TLR4 mutant), either because of a decreased Th2 response to the larvae or because of the absence of a response to Wolbachia. TLR4-mutant mice were immunized against O. volvulus with irradiated third-stage larvae, and it was observed that Th2 responses were elevated based on increased IL-5 production, total immunoglobulin E (IgE) levels, antigen-specific IgG1 response, and eosinophil recruitment. Protective immunity, however, did not develop in the TLR4-mutant mice. The Th1 response, as measured by gamma interferon production from spleen cells, was comparable in both wild-type and TLR4-mutant mice. Furthermore, antibody responses to Wolbachia were absent in both wild-type and TLR4-mutant mice. Therefore, the defect in the development of a protective immune response against O. volvulus in TLR4-mutant mice is not due to loss of Th2 immunity or the response to Wolbachia but is due to an unidentified TLR4-dependent larval killing mechanism.

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The effect of the microfilaricidal drug ivermectin on the antibody response to a detergent extract of adult Onchocerca volvulus (OvAg) and a number of specific recombinant peptides was examined. Three of the peptides were combined in a serodiagnostic 'cocktail' and the effect of ivermectin on the diagnostic performance of this assay was assessed. Immunoglobulin (Ig) G1 serum levels in response to OvAg significantly decreased following ivermectin treatment. The antibody response to only one recombinant peptide (OvMBP29) was significantly affected, with IgG levels decreasing following treatment. Levels of total IgE increased following treatment. No correlation was observed between initial antibody level (or change in antibody level) and any adverse reaction to treatment. The serodiagnostic 'cocktail' was 100% sensitive before and after the use of ivermectin. A serodiagnostic assay using specific recombinant peptides can be used to evaluate infection in the absence of dermal microfilariae in areas where ivermectin is used.

Larvae and adults of Strongyloides ratti were examined for collagenolytic activity on 14C proline-labelled, native, guinea-pig skin collagen substrate. The activity was measured by determining either the amount of hydroxyproline released or the amount of radioactivity in the solubilized fraction of the collagen substrate. Bacterial collagenase was used for enzyme control and trypsin served as substrate control. No collagenolytic activity was found in living larvae, their extracts or metabolites. The collagenolytic activity of the metabolites of adult worms appeared weak, whereas that of the extracts of the adults was pronounced. It is suggested that collagenase is active in the adult females at the time of migration in the intestinal mucosa during oviposition.