Abstract
The local immune mechanisms responsible for the establishment and development of Echinococcus granulosus sensu stricto infection in the liver, have been little explored. We developed a suitable experimental model that mimics naturally infected livers using portal injection of protoscoleces. Opposite to Echinococcus multilocularis infection which is dose-dependent, fully mature hydatid cysts can be established in the liver whatever the injection dose; although most of the infection sites were seen at the establishment phase as inflammatory granulomas associated with fibrosis, they never matured into cysts. At the establishment phase, a strong immune response was composed of T and B cells, with T1-type, T2-type cells and cytokines and IL-10-secreting CD8+ T cells in the liver. At the established phase, results suggested a local production of antibodies by B cells, and an involvement of NK and NKT cells. Infection outcome and local immune response in the liver, were different in the mouse models of Echinococcus granulosus sensu stricto and Echinococcus multilocularis respectively; however, only early specificities at the microenvironment level might explain the major differences found between the lesions induced by the two species. Our quantitative experimental model appears fully appropriate to further study this microenvironment and its relationship with each cestode species.
Highlights
The local immune mechanisms responsible for the establishment and development of Echinococcus granulosus sensu stricto infection in the liver, have been little explored
Immune responses elicited in the liver during experimental secondary infection by E. granulosus s.l., especially those observed at an early stage of infection, have been far less studied than those observed in E. multilocularis infection[12]
Consistent with previous data[18], our study documented that mice were suitable hosts for secondary Cystic echinococcosis (CE) using PSCs obtained from sheep, and the hydatid cysts developing in the liver resembled those of naturally infected human liver in CE and those obtained in Balb/cJ and DBA/2 J mice by using eggs through the oral route[19]
Summary
The local immune mechanisms responsible for the establishment and development of Echinococcus granulosus sensu stricto infection in the liver, have been little explored. We developed a suitable experimental mouse model that mimics naturally infected livers by injection of Echinococcus multilocularis (E. multilocularis) PSCs via the portal vein This model allowed us to study host’s immune response according to the parasite load. Taking benefit from the similarity and quantitative nature of the model of PSC injection in the portal vein for both E. granulosus and E. multilocularis, we investigated the impact of the inoculation of different E. granulosus s.s. PSC numbers (corresponding to low, medium and high dose groups, respectively LDG, MDG and HDG) on the development of the cysts in the liver of C57BL/6 mice, a strain of intermediate susceptibility to both species of Echinococcus, as is observed in humans, and we assessed the relationship between the observed histological aspects, intensity of infection, and liver fibrosis. To study the relationship between infection following increasing number of PSCs and the host’s immune response, and make the immunological profile observed in this model comparable to that previously described in the experimental model of E. multilocularis infection, we measured most of the known cellular and cytokine markers of the immune balance in Echinococcus spp. infection and analyzed whether and how these patterns affected the establishment of infection and parasite growth
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