Epithelial Talin-1 Protects Mice from -induced Colitis by Restricting Bacterial Crypt Intrusion and Enhancing T Cell Immunity

Pathogenic enteric present a significant burden to global health. Food-borne enteropathogenic (EPEC) and Shiga toxin-producing (STEC) utilize attaching and effacing (A/E) lesions and actin-dense pedestal formation to colonize the gastrointestinal tract. Talin-1 is a large structural protein that links the actin cytoskeleton to the extracellular matrix though direct influence on integrins. Here we show that mice lacking talin-1 in intestinal epithelial cells () have heightened susceptibility to colonic disease caused by the A/E murine pathogen . mice exhibit decreased survival, and increased colonization, colon weight, and histologic colitis compared to littermate controls. These findings were associated with decreased actin polymerization and increased infiltration of innate myeloperoxidase-expressing immune cells, confirmed as neutrophils by flow cytometry, but more bacterial dissemination deep into colonic crypts. Further evaluation of the immune population recruited to the mucosa in response to revealed that loss of in colonic epithelial cells (CECs) results in impaired recruitment and activation of T cells. infection-induced colonic mucosal hyperplasia was exacerbated in mice compared to littermate controls. We demonstrate that this is associated with decreased CEC apoptosis and crowding of proliferating cells in the base of the glands. Taken together, talin-1 expression by CECs is important in the regulation of both epithelial renewal and the inflammatory T cell response in the setting of colitis caused by , suggesting that this protein functions in CECs to limit, rather than contribute to the pathogenesis of this enteric infection.