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 in an ameliorated granulomatous reaction and hence a mild disease. This study examined some of the immunological mechanisms that could be associated with 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 cercariae each (group B) given at 3-day intervals. The mice were treated with praziquantel 8 weeks postinfection and, 2 weeks later, together with another group of naive mice (group C), they were infected with a single dose of 100 cercariae each. All the animals were killed 8 weeks later and schistosome egg antigen (SEA)- and soluble adult worm antigen preparation (SWAP)-induced cytokine recall responses in splenocytes, as well as serum immunoglobulin levels, were quantified and hepatic granuloma sizes measured. Group A animals had higher levels of SEA-induced interferon-gamma (IFN-gamma) but lower levels 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 these 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 immunoglobulin E (IgE) and immunoglobulin G (IgG) titres were not significantly different between the three groups. Granuloma diameters were larger in group C (mean 297 +/- 51.3 microm) as compared to groups A (174 +/- 49 microm, P < 0.01) and B (247.5 +/- 44 microm, P < 0.05). Taken together, these results demonstrate that granuloma size is reduced during a reinfection exposure compared with a primary infection. This reduction is associated with a T helper 1 response in mice exposed to a single large dose of cercariae in the primary infection and with a predominantly T helper 2 response in those infected with multiple small doses.
Farah
I O
IO
Division of Comparative Medicine, Department of Physiology, Biomedical Centre, Uppsala University, Sweden.
Johansson
M
M
Lövgren-Bengtson
K
K
Hau
J
J
D000818:Animals; D000909:Antibodies, Helminth / Q000096:biosynthesis / Q000097:blood; D000947:Antigens, Helminth / Q000276:immunology / Q000494:pharmacology; D002478:Cells, Cultured; D003208:Concanavalin A / Q000494:pharmacology; D003470:Culture Media / Q000494:pharmacology; D016207:Cytokines / Q000096:biosynthesis; D005260:Female; D006099:Granuloma / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008109:Liver Diseases, Parasitic / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D011223:Praziquantel / Q000627:therapeutic use; D012008:Recurrence; D012550:Schistosoma mansoni / Q000254:growth & development* / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000188:drug therapy / Q000276:immunology* / Q000469:parasitology* / Q000473:pathology; D013154:Spleen / Q000166:cytology; D018417:Th1 Cells / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology* / Q000378:metabolism
D000909:Antibodies, Helminth; D000947:Antigens, Helminth; D003470:Culture Media; D016207:Cytokines; D003208:Concanavalin A; D011223:Praziquantel