Immunopathology and immune responses to Schistosoma mansoni were examined in IL-4 -/- mice. IL-5 and IL-10 production by lymphoid cells stimulated with soluble egg antigen (SEA), peripheral eosinophilia and serum levels of soluble IL-4 receptor but not IgE were all significantly elevated over background normal levels in IL-4 -/- mice as a result of infection. Additionally, IL-10 and IL-5 in addition to IL-2 and IFN-gamma transcripts were equally evident in diseased liver tissue from infected IL-4 -/- and wild-type mice. Nevertheless, analysis of antigen-stimulated IL-2, IL-4, IL-5, IL-10 and IFN-gamma production by lymphoid organ cells from infected or egg-injected IL-4 -/- mice revealed a more Th1-like pattern of cytokine production (IFN-gamma > IL-5) than in (wild-type) mice in which a stronger type 2 response to SEA was detectable (IL-4, IL-5 > IFN-gamma). Despite this, at 8 and 16 weeks after infection, liver pathology, as indicated by the size, cellularity, cellular composition and collagen content of granulomas, was similar in IL-4 -/- and wild-type animals. As in wild-type animals, granuloma size at week 16 was smaller than at week 8, indicating that modulation had occurred in the absence of IL-4. Differences in pathology were seen only when eggs were experimentally embolized to the lungs, in which case IL-4 -/- mice made smaller granulomatous responses than did wild-type animals. These data clearly show that IL-4 is not necessary for the hepatic granuloma formation which occurs during experimental schistosomiasis.

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The in vitro and in vivo interaction of Schistosoma japonicum with salmonellae and other gram-negative bacteria was studied. In vitro, S. japonicum associated with salmonellae and other gram-negative bacteria, and more male than female schistosomes associated with the bacteria. By using the various strains and mutants of salmonellae, we showed that Salmonella typhimurium had a higher degree of association than did Salmonella enteritidis and that the piliated strains of S. typhimurium associated much more frequently than did the nonpiliated strains. However, in vivo studies demonstrated more frequent association of salmonellae with female than with male schistosomes and that the piliated and nonpiliated strains of salmonella did not differ in their association with the worms.