IL-10 is required for prevention of necrosis in the small intestine and mortality in both genetically resistant BALB/c and susceptible C57BL/6 mice following peroral infection with Toxoplasma gondii

The role for IL-10 in the immunopathogenesis of acute toxoplasmosis followi ng peroral infection was examined in both genetically susceptible C57BL/6 a nd resistant BALB/c mice. C57BL/6-background IL-10-targeted mutant (IL-10(- /-)) mice all died in 2 wk after infection with 20 cysts of the ME49 strain , whereas only 20% of control mice succumbed. Histological studies revealed necrosis in the small and large intestines and livers of infected IL-10(-/ -) mice, The necrosis in the small intestine was the most severe pathologic response and was not observed in control mice. Treatment of infected IL-10 (-/-) mice with either anti-CD4 or anti-IFN-gamma mAb prevented intestinal pathology and significantly prolonged time to death. Treatment of these ani mals with anti-IL-12 mAb also prevented the pathology. Significantly greate r amounts of IFN-gamma, mRNA were detected in the lamina propria lymphocyte s obtained from the small intestine of infected IL-10(-/-) mice than those from infected control mice, In common with C57BL/6-background IL-10(-/-) mi ce, BALB/c-background IL-10(-/-) mice all died developing intestinal pathol ogy after infection. Control BALB/c mice all survived even after infection with 100 cysts and did not develop the intestinal lesions. Treatment with a nti-IFN-gamma mAb prevented the pathology and prolonged time to death of th e infected n-10(-/-) mice, These results strongly suggest that IL-10 plays a critical role in down-regulating IFN-gamma production in the small intest ine following sublethal peroral infection with Toxaplasma gondii and that t his do,vn-regulatory effect of IL-10 is required for prevention of developm ent of IFN-gamma-mediated intestinal pathology and mortality in both geneti cally resistant BALB/c and susceptible C57BL/6 mice.