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T-cell immune responses in the residence and clearance of Echinococcus: role of inoculum size in a quantitative hepatic experimental model

Chuanshan Zhang  Zhide Li  Shuting Yang  Xiaojuan Bi  Hui Wang  Li Liang  Renyong Lin  Hao Wen  
【摘要】:The local immune mechanisms responsible for either self-healing or sustained chronic infection are not clear, in the development of E. multilocularis larvae or E. granulosus. Here, we developed a suitable experimental model that mimics naturally infected livers, according to the parasite load. We demonstrated that local cellular immunity and fibrogenesis are actually protective and fully able to limit metacestode growth in the liver of low or medium dose E. multilocularis PSCs-infected mice(LDG or MDG), or even to clear it, while impairment of cellular immunity is followed by a more rapid and severe course of the disease in high dose-infected mice(HDG). However, injecting with low and medium doses of E. granulosus PSCs could make mice become infected and form hepatic hydatid cysts, similar to high dose infections. And recruitment and/or proliferation of memory T cells(including CD4 Tem, CD8 Tcm and CD8 Tem) and imbalance of T1/T2/T17/Treg-type T cells in liver were not only associated with clearance of the parasite infection in LDG, but also with increased hepatic injury in HDG; in particular the dual role of CD8 T cells depending on the parasite load and the various stages of metacestode growth. Meanwhile, increase in CD4+T cells, the ratio of CD4+/CD8+ T cells and effector of memory CD4 T cells were involved in mediating E. granulosus infection. Besides, we first demonstrate the association between LAG3-or 2 B4-expressing T cells exhaustion and HD inocula in late stages of E. multilocularis-infection. Our findings suggest modulation of the various types of immune response could be a therapeutic strategy for hydatid patients.

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