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.

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-gamma 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-gamma 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-gamma 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-gamma 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-gamma-mediated intestinal pathology and mortality in both genetically resistant BALB/c and susceptible C57BL/6 mice.

• Authors: Y Suzuki, A Sher, G Yap, D Park, L E Neyer, O Liesenfeld, M Fort, H Kang, E Gufwoli
• Journal: Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 164 Issue 10 Pg. 5375-82 (May 15 2000) ISSN: 0022-1767 [Print] United States
• PMID: 10799901 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antibodies, Monoclonal
• Antigens, Protozoan
• CD4 Antigens
• Interleukin-10
• Interleukin-12
• Interferon-gamma

Topics

• Administration, Oral
• Animals
• Antibodies, Monoclonal (administration & dosage)
• Antigens, Protozoan (administration & dosage, immunology)
• CD4 Antigens (immunology)
• Dose-Response Relationship, Immunologic
• Female
• Genetic Predisposition to Disease
• Immunity, Innate
• Injections, Intraperitoneal
• Interferon-gamma (biosynthesis, immunology)
• Interleukin-10 (deficiency, genetics, physiology)
• Interleukin-12 (immunology)
• Intestinal Diseases, Parasitic (genetics, immunology, mortality, pathology)
• Intestinal Mucosa (immunology, metabolism)
• Intestine, Small (immunology, metabolism, pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• Mice, Knockout
• Necrosis
• Survival Analysis
• Time Factors
• Toxoplasma (immunology)
• Toxoplasmosis, Animal (genetics, immunology, mortality, pathology)