Cellular Tight Junctions Prevent Effective Invasion and Inflammatory Barrier Disruption Promoting Bacterial Invasion from Lateral Membrane in Polarized Intestinal Epithelial Cells.

invasion is closely related to pathogenicity. The intestinal epithelium contains polarized epithelial cells that form tight junctions (TJs) to provide a physical barrier against bacterial invasion. Previous studies indicated that invasion of non-polarized cells involves several cellular features, including lipid rafts. However, the dynamics of invasion of polarized epithelial cells are not fully understood. Here we investigated the interaction between invasion and TJ formation to characterize the mechanism of invasion in polarized epithelial cells. In contrast to non-polarized epithelial cells, invasion was not affected by depletion of lipid rafts in polarized epithelial cells. However, depletion of lipid rafts significantly decreased invasion in TJ disrupted cells or basolateral infection and repair of cellular TJs suppressed lipid raft-mediated invasion in polarized epithelial cells. In addition, pro-inflammatory cytokine, TNF-α treatment that induce TJ disruption promote invasion and lipid rafts depletion significantly reduced invasion in TNF-α treated cells. These data demonstrated that TJs prevent invasion from the lateral side of epithelial cells, where they play a main part in bacterial invasion and suggest that invasion could be increased in inflammatory condition. Therefore, maintenance of TJs integrity should be considered important in the development of novel therapies for infection.