The role for IL-10 in the immunopathogenesis of acute toxoplasmosis following peroral infection was examined in both genetically susceptible C57BL/6 and 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-γ mAb prevented intestinal pathology and significantly prolonged time to death. Treatment of these animals with anti-IL-12 mAb also prevented the pathology. Significantly greater amounts of IFN-γ mRNA were detected in the lamina propria lymphocytes obtained from the small intestine of infected IL-10−/− mice than those from infected control mice. In common with C57BL/6-background IL-10−/− mice, BALB/c-background IL-10−/− mice all died developing intestinal pathology after infection. Control BALB/c mice all survived even after infection with 100 cysts and did not develop the intestinal lesions. Treatment with anti-IFN-γ mAb prevented the pathology and prolonged time to death of the infected IL-10−/− mice. These results strongly suggest that IL-10 plays a critical role in down-regulating IFN-γ production in the small intestine following sublethal peroral infection with Toxoplasma gondii and that this down-regulatory effect of IL-10 is required for prevention of development of IFN-γ-mediated intestinal pathology and mortality in both genetically resistant BALB/c and susceptible C57BL/6 mice.
CITATION STYLE
Suzuki, Y., Sher, A., Yap, G., Park, D., Neyer, L. E., Liesenfeld, O., … Gufwoli, E. (2000). 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 Journal of Immunology, 164(10), 5375–5382. https://doi.org/10.4049/jimmunol.164.10.5375
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