The Schistosoma mansoni egg-derived r38 peptide-induced Th1 response affects the synchronous pulmonary but not the asynchronous hepatic granuloma growth.
The p38 peptide derived from Schistosoma mansoni egg-antigens (SEA) is a preferential inducer of the Th1 response. In the present study, we investigated whether induction of a p38-specific Th1 or Th2 response can influence granuloma development in infected or sensitized mice. Mice sensitized with SEA/IL-12 3 weeks after infection but before worm oviposition commenced developed Th1 cytokine responses and had significantly reduced hepatic granuloma size. Similar immunization with p38/IL-12 induced a strong peptide-specific Th1, mixed SEA-specific Th1/Th2 responses without effect on hepatic granuloma development. Presentation of p38 with alum or alum/IL-12 mixture enhanced Th2 cytokine responses and hepatic granuloma sizes. In the synchronized pulmonary model, sensitization of naïve mice with p38/IL-12 induced a strong Th1 cytokine production to p38 and SEA, led to a moderate increase in granuloma growth at days 4 and 8 following egg injection and actually promoted the resolution of the lesion by day 16. Sensitization with p38 in alum induced Th2 cytokine production and generated the largest granulomas whereas the p38/alum/IL-12 sensitized group showed intermediate results in cytokine production and granuloma growth. Thus, in infected mice, the p38 induced strong Th1 response was insufficient to cross-regulate the evolving Th2 environment that generated large granulomas.
Chen
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Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
Boros
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D000818:Animals; D000947:Antigens, Helminth / Q000276:immunology*; D005260:Female; D006099:Granuloma / Q000276:immunology*; D007114:Immunization; D018664:Interleukin-12 / Q000276:immunology; D008099:Liver / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008109:Liver Diseases, Parasitic / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D008174:Lung Diseases, Parasitic / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D051379:Mice; D008808:Mice, Inbred CBA; D010455:Peptides / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D012550:Schistosoma mansoni / Q000254:growth & development / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology* / Q000517:prevention & control; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology
D000947:Antigens, Helminth; D010455:Peptides; D011994:Recombinant Proteins; D018664:Interleukin-12