Infectivity and Pathological Changes in Murine Clonorchiasis: Comparison in Immunocompetent and Immunodeficient Mice

Abstract

The main complications of clonorchiasis are periportal inflammation, biliary hyperplasia, periductal fibrosis, and subsequently the development of biliary tumors in the liver. This study was undertaken to compare the infectivity and histopathologic changes between in immunocompetent FVB/NJ and BALB/cA strains, and immunodeficient severe combined immunodeficient (SCID) and athymic nude mice after the metacercariae of Clonorchis (C.) sinensis were infected. The experiment showed that C. sinensis was very infective in all strains studies, but the status of worm development, infectivity, recovery rate, and morphological changes of livers were very different in each strain. FVB/NJ mice showed more worm recovery than any other strain. Histopathologically the liver of FVB/NJ mice at 4 weeks postinfection showed marked cystic and fibrotic changes, in which C. sinensis was fully developed with ovum production, severe infiltration of inflammatory cells, mostly eosinophils, and high degrees of biliary hyperplasia. In SCID and nude mice, there were few foci of inflammatory cells even at 8 weeks postinfection in periportal areas of the liver, associated with no development into adult worm with ovum production. Fibrosis occurring at 4 weeks postinfection was highly correlated with inflammatory infiltration when each strain was compared. We suggest that massive infiltration of eosinophil and plasma cells caused by the infection might initiate cystic formation and fibrosis. These data demonstrate that the infection of C. sinensis might be related to pathologic consequences of inflammatory cell infiltration, cystic formation and fibrosis which might play a role in the defense mechanism against the parasitism in the liver of each strain. The FVB/NJ mouse model might be very helpful in elucidating the mechanism for human clonorchiasis.