Brugia malayi: acquired resistance to microfilariae in BALB/c mice correlates with local Th2 responses

The role of specific Th subsets in the regulation of acquired resistance to the filarial parasite Brugia malayi is not known. We examined pathologic and cytokine responses in filarial antigen-sensitized BALB/c mice inoculated intraperitoneally with live microfilariae. Animals immunized three times with soluble microfilarial antigen demonstrated accelerated clearance of live parasites (12 +/- 5% of parasites recovered from the peritoneal cavity 4 days after inoculation vs 57 +/- 6% in controls, P < 0.001). Elimination of microfilariae by immunized mice was associated with local eosinophilia (1.5 x 10(7) eosinophils/ml peritoneal wash fluid compared with 2 x 10(5) eosinophils/ml in unimmunized animals), development of local eosinophil-containing granulomas, and elevated serum IgE levels (7.0 +/- 1.4 vs 2.1 +/- 0.9 micrograms/ml in controls, P < 0.01). CD4+ cells from the site of parasite challenge produced Th2-associated cytokines exclusively (IL-4 and IL-5, not IFN-gamma and IL-2) in response to Brugia antigen, whereas spleen and lymph node cells produced both Th1- and Th2-associated cytokines. Mice immunized a single time with microfilarial antigen did not clear parasites in this time, and peritoneal exudate cells from these animals produced IFN-gamma but not IL-5. These results indicate that acquired resistance to B. malayi microfilariae in mice is associated with induction of a Th2 and not a Th1 response at the site of parasite elimination.