Impaired natural defence of beige (Chediak-Higashi syndrome) mice against tissue-migrating larvae of Strongyloides ratti and its reconstitution by bone marrow cells.

The susceptibility of C57BL/6-bgJ/bgJ mice, which exhibit a murine counterpart of the Chediak-Higashi syndrome, to infection with Strongyloides ratti was examined. After a primary infection, the peak of the daily larval output in faeces (LPG) of bgJ/bgJ mice was approximately twice as high as that of their littermate bgJ/+mice. The total number of tissue migrating larvae recovered from bgJ/bgJ mice at 36 h after infection was also approximately twice as high as that from bgJ/+mice. However, after a primary infection, bgJ/bgJ mice could completely expel adult worms in the intestine by day 14. When an equal number of tissue migrating larvae obtained from the head of +/+ mice were implanted into bgJ/bgJ and bgJ/+mice, the magnitude and the kinetics of LPG were comparable between them, indicating that in both groups implanted larvae established in the intestine to become adult worms and then they were expelled by day 13. Thus, immune mechanisms involved in worm expulsion of bgJ/bgJ mice were comparable to those of bgJ/+mice. The higher susceptibility of bgJ/bgJ mice could be reduced to the level of bgJ/+mice by bone marrow grafting from bgJ/+mice 6 weeks prior to infection. Furthermore, when lethally irradiated bgJ/bgJ mice or bgJ/+mice were reconstituted with either type of bone marrow cells, the mice given bgJ/bgJ bone marrow cells showed higher susceptibility to infection with S. ratti regardless of the genotype of the recipients. These results indicate that the impaired natural defence of bgJ/bgJ mice is predetermined at the level of haemopoietic stem cells.