Absence of weight loss during Cryptosporidium infection in susceptible mice deficient in Fas-mediated apoptosis.
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.
Motta
Iris
I
Unité de Biologie Moléculaire du Gène, Inserm 277, Université Paris 7, Institut Pasteur, 25, rue du Dr. Roux, 75724 Paris cedex 15, France.
Gissot
Mathieu
M
Kanellopoulos
Jean M
JM
Ojcius
David M
DM
D000818:Animals; D017209:Apoptosis; D001835:Body Weight; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003457:Cryptosporidiosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D016785:Cryptosporidium parvum; D053222:Fas Ligand Protein; D005260:Female; D015870:Gene Expression; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D019463:Mice, Inbred MRL lpr; D018345:Mice, Knockout; D015431:Weight Loss
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins