The role of epithelial caspase-8 during infection with Salmonella typhimurium

Deficiency of caspase-8 in intestinal epithelial cells (IECs) of mice leads to spontaneous ileitis and increased sensibility towards DSS-induced colitis. We now investigated the role of epithelial caspase-8 in infectious colitis. Therefore we infected Caspase-8^ΔIEC mice with Salmonella typhimurium. In contrast to wild type mice, Caspase-8^ΔIEC mice showed a high lethality after infection. Excessive cell death and the following barrier breakdown enable the commensal gut microbiota to invade into subepithelial areas, resulting in a systemic infection. This might be caused by the absence of Paneth cells and a reduced number of goblet cells in the intestine, which both have a crucial role in the antimicrobial defense and therefore maintaining the mucosal barrier in the gut. RNA data did not show an altered expression of antimicrobial peptides in the colon of control versus Caspase-8^ΔIEC mice challenged with Salmonella typhimurium. This suggests that probably an altered intestinal microflora, which is present in Caspase-8^ΔIEC mice, might enable Salmonella typhimurium to replicate more extensively. Our data demonstrate a crucial role for caspase-8 in controlling intestinal homeostasis in response to infectious colitis.