Immune response and immunopathology in ICOSL knockout mice infected with Schistosoma japonicum / 中国人兽共患病学报

ABSTRACT

To determine immune responses and immunopathology in ICOSL knockout (ICOSL KO) mice infected with Schistosoma japonicum,ICOSL- KO mice and wild-type C57BL/6J mice were used as experimental models for Schistosoma japonicum infection.The splenic lymphocytes were isolated from the mice the day before infection (0 week) as well as 4,7,12,16 and 20 weeks post infection,and stimulated with SEA for 72 hours in culture.The concentrations of Th1 cytokines (IFN-γand IL- 12) and Th2 cytokines (IL- 4,IL-10 and IL-13) in the culture supernatants were measured by sandwich ELISA.The levels of SEA-specific IgG antibody and its subtypes (IgG1 and IgG2a) were measured in mouse sera by ELISA.Pathological changes of hepatic granuloma in mice were determined by hematoxylin and eosin (H&E) staining.After the infection,the levels of Th1 cytokines,IFN- γ and IL 12,in ICOSL- KO mice were higher than those in wild-type C57BL/6J mice.However,the levels of Th2 cytokines (IL- 4,IL- 10 and IL- 13) were significantly decreased in ICOSL-KO mice compared to those in wild-type C57BL/6J mice.The levels of SEA-specific IgG antibody and its subtypes (IgG1 and IgG2a) in the sera of ICOSL- KO mice were also significantly lower than those of wild -type C57BL/6J mice.Moreover,the Th2 differentiation index was lower in ICOSL- KO mice than in wild-type C57BL/6J mice at 4,7,12,16 and 20 weeks post-infection.Similarly,the ratio of IgG1/IgG2a in ICOSL-KO mice was significantly lower than that in wild- type C57BL/6J mice at 7,12 and 16 weeks post- infection.Furthermore,throughout the course of disease progression,the volume of hepatic egg granuloma in ICOSL- KO mice was significantly smaller than that in wild-type C57BL/6J mice.In conclusions,there is a substantially down-regulated Th2 immune response in ICOSL- KO mice infected with Schistosoma japonicum,thus results in an attenuated hepatic lesion caused by egg granulomas.The findings indicate that the ICOS ICOSL co-stimulatory pathway plays an important role in the hepatic egg granuloma formation of schistosomiasis.