Beschreibung:
<jats:title>Abstract</jats:title>
<jats:p>C. rodentium is a mucosal pathogen of mice that shares several pathogenic mechanisms with enteropathogenic Escherichia coli (EPEC) and enterohaemorrhagic E. coli (EHEC), which are two clinically important human gastrointestinal pathogens. The C. rodentium model of infection is used to study host pathogen interactions in the gastrointestinal tract and to study ulcerative colitis (UC). Mutations in unfolded protein response (UPR) pathways have been linked to a higher risk of UC development. The ER is an important organelle for protein synthesis and protein folding. Dysregulation of ER stress results in the activation of the UPR to restore homeostasis. Chop is activated downstream of the PERK arm of the UPR and is a transcription factor for multiple targets including cell death and inflammatory pathways. We hypothesized that Chop activation increases cell death and inflammation during C. rodentium infection which then promotes infection and tissue damage. We found that when a mouse epithelial cell line was treated with an ER stress inducing drug or C. rodentium there was an upregulation of Il6 and Il23 but when we inhibited Chop expression the upregulation was lost. We next infected Chop knockout mice with C. rodentium and these mice showed less colon pathology and colon colonization at Day 10. These data suggest that Chop has a role in the ability of C. rodentium to trigger inflammation and in tissue pathology.</jats:p>