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

E Pearlman, W K Kroeze, F E Hazlett, S S Chen, S D Mawhorter, W H Boom, J W Kazura
Experimental Parasitology 1993, 76 (2): 200-8
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.

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