In addition to the effects of enterocyte TLR4 activation on the regulation of intestinal injury and repair, our group also has demonstrated a surprising role for enterocyte TLR4 in the regulation of bacterial translocation across the intestinal barrier (see Figure 1A ). Translocation of bacteria across the intestinal barrier is important in the pathogenesis of not only intestinal inflammation, but also systemic sepsis, and may be a critical determinant of the development of multisystem organ dysfunction. We recently have shown that enterocyte TLR4 plays a key role in regulating the ability of enterocytes to internalize Gram-negative bacteria into membrane-bound phagosomes. Further evidence that TLR4 signaling is both necessary and sufficient for phagocytosis by epithelial cells was found as cultured enterocytes were able to internalize LPS-coated but not uncoated latex particles, and MD2/TLR4-transfected HEK-293 cells acquired the capacity to internalize E. coli, whereas non-transfected HEK-293 and HEK-293 transfected with dominant negative TLR4 bearing a P712H mutation did not. Strikingly, the internalization of Gram-negative bacteria into enterocytes in vivo and the translocation of bacteria across the intestinal epithelium to mesenteric lymph nodes were significantly greater in wild-type mice as compared with mice with mutations in TLR4 (27) . These data suggest a novel mechanism by which bacterial translocation occurs, and suggest a critical role for TLR4 in the phagocytosis of bacteria by enterocytes in this process.