Gut Epithelial Lining Makes the First Move

The mucosal immune system is ruled by a distinctive set of mechanisms derived of the local microenvironment demands. Intestinal epithelial cells (IECs) represent a unique population of cells that exist in direct contact with a burden of bacteria and provide a primary physical barrier between the antigenic overload of the lumen and leukocytes settled in the lamina propria. The cross talk between these compartments maintains the intestinal homeostasis. The network of dendritic cells (DCs) in the vicinity of IECs is crucial in this process as DC maturation across the epithelial barrier seems to be dependent on the presence of specific surface factors. IECs are broadly unresponsive to gram-positive bacterial components, notably TLR-2 ligands, in contrast to gram-negative bacterial components. The TLR signaling is tightly regulated in IECs to avoid uncontrolled inflammation by several negative regulators that include IAP, A20, NOD2, and IRAK-M.