Physiol 283: G833–G839, 2002; 10.1152/ajpgi. 00208.2002.—The intestinal epithelial cell (IEC) is exposed at the apical surface to a high concentration of foreign antigen and bacterial products capable of triggering inflammatory responses. Complex intracellular pathways of antigen trafficking and the polarized expression of immunologically active receptors provide additional means to regulate the inflammatory pathways in these cells. In the case of human leukocyte antigen (HLA) class II heterodimers, surface expression is highly restricted to the basolateral surface, and this also appears to be the case for Toll-like receptor 5 (TLR5) on polarized T84 human colon cancer cells. Processing of soluble antigen via HLA class II in IEC can occur following internalization from the apical surface but is highly inefficient. In addition, certain bacteria can facilitate the transport of flagellin (the ligand for TLR5) across an intact epithelium. Disruption of the tight junctions between IECs, allowing direct access of antigen and flagellin to the basolateral surface of the cell, dramatically affects the functional outcome HLA class II and TLR5 pathways. cell polarity; intestinal epithelium; flagellin; lipopolysaccharide

THE IMMUNOLOGIC CHALLENGE faced along the mucosal surface of the gastrointestinal (GI) tract is extraordinary. In the colon, for example, the microbial burden is estimated to be 109 organisms present per milliliter of lumenal content. Across the vast majority of the surface area of the GI tract, a single layer of polarized epithelial cells separates this vast amount of antigenic material from the underlying gut-associated lymphoid