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Mice infected by syringe inoculation with the L3 of the filarial nematode Brugia pahangi generate a strong Th2 response. In this study we compared immune responses in mice infected via syringe with those infected by mosquito transmission of L3. Levels of antigen-specific IL-4, IL-5 and IL-10 were significantly reduced in mice infected via mosquito. A possible explanation of these results was that mice infected via mosquito received fewer L3 than those infected via syringe. To investigate this possibility, mice were infected with different numbers of L3 (50, 25 or 10). However there was no difference in responses in these animals, suggesting that the reduced immune reactivity in mice infected by mosquito cannot be solely ascribed to exposure to lower numbers of parasites. These results also demonstrate that the L3 is an extremely potent stimulus for Th2 differentiation, with 10 L3 sufficient to drive a strong Th2 response. The differences in immune reactivity between syringe and mosquito infected mice may relate to the presence of immuno-suppressive factors in mosquito saliva inoculated at the time of transmission or may reflect the interaction of L3 with different populations of antigen presenting cells in the two groups of mice. Further studies will be required to differentiate between these possibilities.

Sub-cutaneous infection of interleukin (IL)-4-/- mice on the BALB/c background with third stage larva (L3) of Brugia pahangi revealed an altered cytokine profile consistent with the absence of the Th2 promoting cytokine IL-4. Splenocytes from IL-4-/- mice secreted significantly more antigen (Ag)-specific IL-2 and interferon-gamma and significantly less Ag-specific IL-5, compared to those from L3-infected wild-type mice. However, levels of Ag-specific IL-13 were similar between groups. Despite the alteration in immune responses, there was no significant difference in recovery of developing worms from the peritoneal cavity of the two strains of mice at any time postinfection. However, at later time points of infection, the IL-4-/- mice contained large numbers of microfilariae (Mf) in the peritoneal cavity while the wild-type mice contained comparatively few Mf. The differences in Mf levels appear to relate to differences in worm fecundity in the two strains of mice, with adult female worms from the wild-type mice containing few developing Mf. Moreover, implantation of sexually mature adult female worms into the peritoneal cavity of both strains of mice resulted in equal levels of Mf, confirming that the primary role of IL-4 is to limit fecundity during the maturation phase of infection.