Figure 2.

Epithelial innate immune function is a key factor in maintaining gut homeostasis. IECs express PRRs, such as TLRs and NOD-like receptors, whose signaling activates NF-κB, leading to reinforcement of the epithelial barrier through release of anti-microbial peptides (i.e., defensins) and paracellular secretion of proinflammatory cytokines (e.g., TNF, IL-1, and IL-18) that enhance mucosal defense to bacterial penetration and the production of trophic factors, such as intestinal TFF3 that can block IEC apoptosis. Autophagy, perhaps due to ATG16L1, also contributes to the effectiveness of the epithelial barrier, controlling intracellular pathogens, and inducing lysozyme production. Breakdown of PRR/NF-κB signaling pathways via critical components, including MyD88, TAK1, and NEMO, facilitates penetrance of luminal microorganisms, triggering an exaggerated adaptive immune response. Similarly, defects in autophagy lead to less effective bacterial clearance and production of proinflammatory molecules, such as adipokines and acute phase reactants from Paneth cells.