Absence of weight loss during Cryptosporidium infection in susceptible mice deficient in Fas-mediated apoptosis.

Abstract Apoptosis plays a major role in the development of pathogenesis due to a number of microbial infections. Epithelial cells have been previously shown to die through apoptosis during in vitro infection by the Apicomplexan parasite Cryptosporidium parvum . We now test the possibility that Fas (APO-1/CD95)-dependent apoptosis of uninfected cells, due to enhanced expression of the Fas ligand (FasL) on infected cells, may contribute to the pathology of cryptosporidiosis. Expression of the FasL increased by a large amount on the surface of intestinal epithelial cells infected with C .  parvum , and the increase was limited exclusively to infected cells. In addition, a significant increase in FasL expression was observed in epithelial cells from the small intestine of mice infected with C .  parvum . Finally, whereas wild-type mice depleted of CD4 + lymphocytes lost weight during C .  parvum infection, CD4 + cell-depleted lpr mice (deficient in Fas function) infected with C .  parvum gained weight at the same rate as undepleted wild-type or lpr mice. These results suggest that bystander Fas-dependent apoptosis of uninfected epithelial cells may exacerbate the weight loss associated with cryptosporidiosis.