Variation of hepatic fibrosis and granuloma size among mouse strains infected with Schistosoma mansoni.

To investigate the relation between the size of circumoval granulomas and hepatic fibrosis, a variety of mouse strains infected with Schistosoma mansoni were examined and the number of eggs in the tissues, the fibrotic responses to the eggs, and the volume of the granulomas were determined. Marked differences in granuloma volume and in hepatic fibrosis were found between mouse strains, and those strains with the largest granulomas also showed the most hepatic fibrosis. On the other hand no significant correlation between granuloma size and hepatic fibrosis was found in the progeny of the F2 generation and backcrosses between F1 mice and the parental strains when crosses were made between Nmri mice (high granuloma volume and high fibrosis) and C57BL/6 mice (low granuloma volume and low fibrosis). Hepatic fibrosis per egg decreased with increasing infection intensity while granuloma volume was unaffected, indicating that fibrosis and granuloma size are at least in part modulated by different factors. The number of eggs found in the tissues per worm pair and the proportion of eggs in the liver also decreased as infection intensity increased. Some influence of the major histocompatibility complex on both granuloma size and fibrosis was found. Congenic mice on the C57BL/10 and C3H/HeSn backgrounds showed larger granulomas in H-2b than in H-2k mice, but no such correlation was found in comparing C57BL/6 mice with B6.H-2k mice. Less hepatic fibrosis was found in B10.M (H-2f), B10.SM (H-2v), and B10.RIII (H-2r) animals than in C57BL/10 mice. The regulation of granuloma size and of hepatic fibrosis is clearly complex and involves genes both outside of and within the major histocompatibility complex.

Differences in hepatic fibrosis and granuloma size in several strains of mice infected with Schistosoma japonicum.

Mice of several strains were exposed to Schistosoma japonicum cercariae and killed 6, 7, 10, or 15 weeks later. Hepatic fibrosis was consistently most marked in ICR mice and least marked in C57BL/6, A and C57BL/Ks mice. Intermediate degrees of fibrosis were present in C3H, CBA and Nmri mice. The size of circumoval granulomas also varied greatly among mouse strains but the degree of hepatic fibrosis was unrelated to granuloma size, indicating that the mechanisms regulating granuloma size may not be relevant to other important parameters of pathology induced by schistosome infection. The degree of fibrosis in S. japonicum-infected ICR mice is similar to that measured in S. japonicum-infected rabbits but is less than that in S. mansoni-infected mice.

Hepatic fibrosis in Schistosoma haematobium-infected mice.

Swiss mice were exposed subcutaneously to 270 to 500 Schistosoma haematobium cercariae and killed 13 to 52 weeks later. Less than 10% of applied cercariae were recovered as worms, and the rate of oviposition by adult worm pairs was generally low. However, the adult worms survived well, the females contained an average of 56 eggs one year after infection, and numerous mature eggs were present in the tissues. All worms were located in the portal venous system. S. haematobium eggs in the liver elicited marked fibrosis, comparable to the fibrosis induced by S. mansoni infection. Only minimal fibrosis is seen around S. haematobium eggs in the liver of numerous other species, including man, the chimpanzee, other non-human primates and hamsters. Our findings illustrate the diverse relationships often seen between a single schistosome species and its mammalian hosts and emphasize the uncertainty in predicting the outcome of human schistosome infections from the study of experimental hosts.