Title

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

ORCiD

David M. Ojcius: 0000-0003-1461-4495

Document Type

Article

Publication Title

Microbes and Infection

ISSN

1286-4579

Volume

4

Issue

8

DOI

10.1016/S1286-4579(02)01602-7

First Page

821

Last Page

827

Publication Date

7-1-2002

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.