Fas receptor (CD95, TNFR6) is a member of the TNF receptor superfamily and is best characterized for its ability to induce extrinsic apoptosis upon ligation of its ligand, FasL. Following Fas activation, Fas-associated protein with death domain (FADD) and caspase-8 are recruited to the receptor to form the death-inducing signalling complex (DISC). Fas-FasL interactions are crucial in the maintenance of immune homeostasis.
Recent work in our laboratory shows that the intestinal pathogen, Enteropathogenic E. coli (EPEC) secretes an effector protein, NleB, into epithelial cells which targets FADD and ablates FasL mediated caspase-8 activation. Fas is expressed on the basolateral surface of intestinal epithelial cells, however the purpose of Fas-FasL interactions (homeostatic or immune regulatory) in this cell type is unclear. Infection of C57BL/6 mice with the model organism Citrobacter rodentium, deficient in nleB, shows impaired colonization compared to wild-type C. rodentium, indicating that the inhibition of Fas signalling in the intestinal epithelium by NleB is critical for the bacteria to establish fulminant disease.
This study interrogates the role of Fas signalling in controlling mucosal infections. In particular, we clarify the key cell types which expressing Fas and FasL interact with each other to control C. rodentium infection.