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

Yasuhiro Suzuki, Alan Sher, George Yap, Daniel Park, Lauri Ellis Neyer, Oliver Liesenfeld, Madeline Fort, Hoil Kang, Edgar Gufwoli

Research output: Contribution to journalArticlepeer-review

193 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)5375-5382
Number of pages8
JournalJournal of Immunology
Volume164
Issue number10
DOIs
StatePublished - May 15 2000

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this