Elevated type 1, diminished type 2 cytokines and impaired antibody response are associated with hepatotoxicity and mortalities during Schistosoma mansoni infection of CD4-depleted mice.
During murine Schistosoma mansoni infections parasite eggs evoke a type 2 cytokine-dependent and CD4(+) T cell-mediated granulomatous response in the liver. In this study CD4(+) T cell-depleted CBA / Ca mice developed hepatic steatosis and had high mortalities during early acute schistosome infection. CD4-depleted mice had smaller liver granulomas and reduced hepatic fibrosis. The hepatocytotoxicity was characterized by microvesicular steatosis and neutrophil infiltration. The livers of depleted mice had similar levels of apoptosis as control infected mice but had a marked increase in lipid peroxidation indicative of their livers being under oxidative stress. CD4-depleted mice had impaired egg excretion and exacerbated intestinal pathology. A type 1 cytokine-dominated response was present in infected CD4-depleted mice and relatively reduced production of type 2 cytokines. Antibody responses to parasite antigens were also substantially reduced. Transfer of immune serum or IgG significantly delayed mortalities in depleted mice and prevented hepatocyte damage. Although biasing the cytokine dichotomy to a type 1-dominated response during murine schistosome infection is desirable with respect to certain pathological processes, i. e. it will reduce the granulomatous inflammation and hepatic fibrosis, these effects contribute to fatal pathology if there is reduced protective type 2 cytokines and a defect in antibody responses.
Fallon
P G
PG
Department of Pathology University of Cambridge, Cambridge, Great Britain. pgf2@cam.ac.uk
Richardson
E J
EJ
Smith
P
P
Dunne
D W
DW
D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology*; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D007109:Immunity; D008099:Liver / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D012550:Schistosoma mansoni / Q000276:immunology*; D012555:Schistosomiasis mansoni / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
D000909:Antibodies, Helminth; D015704:CD4 Antigens; D016207:Cytokines