Secondary Echinococcus multilocularis infection in A/J mice: delayed metacestode development is associated with Th1 cytokine production

Abstract

The course of Echinococcus multilocularis infection was studied in four different strains of mice after intrahepatic inoculation of a metacestode homogenate. Among these strains of mice, A/J and BALB/c mice were characterized, respectively, as the most resistant and susceptible strains. Although there was no significant difference between the mean surface of hepatic metacestodes of these two strains of mice at any examination time, 13 weeks after infection, the mean metastatic burden of A/J mice was significantly lower than that of BALB/c mice. Moreover, at this time, some BALB/c mice spontaneously died from their infection whereas all A/J mice remained in good health. The relative resistance of A/J mice to parasite development was associated with a strong and sustained in vitro spleen cell proliferative response to a crude E. multilocularis extract as well as with a high parasite-induced production of IFN-gamma and IL-2. The susceptibility of BALB/c mice was on the contrary associated with a high IL-4 production. Interestingly, the parasite extract also stimulated a significant IL-4 production by spleen cells of uninfected susceptible BALB/c mice, but not by control A/J mouse spleen cells. Altogether, these results suggest that the relative resistance of A/J mice to E. multilocularis growth is associated with the development of T cell responses characterized by the production of high levels of Th1 cytokines.