Schistosoma mansoni in mice: the pattern of primary cercarial exposure determines whether a secondary infection post-chemotherapy elicits a T helper 1-or a T helper 2-associated immune response

Reinfection with Schistosoma mansoni following chemotherapy often results i n an ameliorated granulomatous reaction and hence a mild disease. This stud y examined some of the immunological mechanisms that could be associated wi th this residual protection. BALB/c mice were infected with either a single dose (group A) of 100 S. mansoni cercariae or with 10 doses of 10 cercaria e each (group B) given at 3-day intervals. The mice were treated with prazi quantel 8 weeks postinfection and, 2 weeks later, together with another gro up of naive mice (group C), they were infected with a single dose of 100 ce rcariae each. All the animals were killed 8 weeks later and schistosome egg antigen (SEA)- and soluble adult worm antigen preparation (SWAP)-induced c ytokine recall responses in splenocytes, as well as serum immunoglobulin le vels, were quantified and hepatic granuloma sizes measured. Group A animals had higher levels of SEA-induced interferon-gamma (IFN-gamma) but lower le vels of interleukin (IL)-5 than groups B and C (P < 0.01). Group B animals had low SEA-induced IFN-gamma levels and elevated IL-5 levels, although the se were lower than group C. SEA-induced IL-10 was low in both groups A and B as compared to group C (P < 0.01). SWAP was less effective as an inducer of splenocyte cytokine production than SEA but both SWAP-induced IFN-gamma and IL-5 were detected in groups A and C. SEA- and SWAP-specific immunoglob ulin E (IgE) and immunoglobulin G (IgG) titres were not significantly diffe rent between the three groups. Granuloma diameters were larger in group C ( mean 297 +/- 51.3 mu m) as compared to groups A (174 +/- 49 mu m, P < 0.01) and B (247.5 +/- 44 mu m, P < 0.05). Taken together, these results demonst rate that granuloma size is reduced during a reinfection exposure compared with a primary infection. This reduction is associated with a T helper 1 re sponse in mice exposed to a single large dose of cercariae in the primary i nfection and with a predominantly T helper 2 response in those infected wit h multiple small doses.