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Listeria monocytogenes is responsible for severe food-borne infections, but the mechanisms by which bacteria cross the intestinal barrier are unknown. Listeria monocytogenes expresses a surface protein, internalin, that interacts with a host receptor, E-cadherin, to promote entry into human epithelial cells. Murine Ecadherin, in contrast to guinea pig E-cadherin, does not interact with internalin, excluding the mouse as a model for addressing internalin function in vivo. In guinea pigs and transgenic mice expressing human E-cadherin, internalin was found to mediate invasion of enterocytes and crossing of the intestinal barrier. These results illustrate how relevant animal models for human infections can be generated.
Understanding how bacteria cross the intestinal barrier is a key issue in the study of foodborne diseases. Listeria monocytogenes causes listeriosis, an infection characterized by bacterial dissemination from the intestinal lumen to the central nervous system and the fetoplacental unit (1). As recently shown, L. monocytogenes is also responsible for gastroenteritis (2, 3). How this bacterium crosses the intestinal barrier is unknown. In vitro, the L. monocytogenes surface protein internalin promotes bacterial internalization into human epithelial cells (4). Its receptor is E-cadherin (5), a protein that mediates the formation of adherens junctions between epithelial cells and is also expressed on the basolateral face of polarized epithelial cells (6). In contrast to human E-cadherin (hEcad), mouse and rat E-cadherins are not receptors for internalin, and internalin plays no role in entry into mouse and rat epithelial cells (7). We have shown that this specificity relies on the nature of the sixteenth amino acid, a proline in hEcad, and a glutamic acid in mouse and rat E-cadherins (7). We concluded that although rat and mouse can be successfully used to study the T cell response to intravenous (IV) infection of L. monocytogenes, they are inappropriate models for studying internalin function in vivo. In mice, oral infections are not reproducibly lethal, and bacterial translocation across the intestinal barrier is low. Moreover, in these animals, specific targeting to the brainstem and the fetoplacental unit is not seen, even after IV inoculation.
Guided by the pioneering work of Racz et al. (8), we observed that a guinea pig epithelial cell line allows entry of L. monocytogenes strain EGD at an efficiency 200 times that...