Uptake of by Intestinal Epithelia.

Background: () can cause different pathologies, e.g., Whipple's disease and transient gastroenteritis. The mechanism by which the bacteria pass the intestinal epithelial barrier, and the mechanism of -induced gastroenteritis are currently unknown.

Methods: Using ex vivo disease models comprising human duodenal mucosa exposed to in Ussing chambers, various intestinal epithelial cell (IEC) cultures exposed to and a macrophage/IEC coculture model served to characterize endocytic uptake mechanisms and barrier function.

Results: exposed ex vivo to human small intestinal mucosae is capable of autonomously entering IECs, thereby invading the mucosa. Using dominant-negative mutants, uptake was shown to be dynamin- and caveolin-dependent but independent of clathrin-mediated endocytosis. Complementary inhibitor experiments suggested a role for the activation of the Ras/Rac1 pathway and actin polymerization. -invaded IECs underwent apoptosis, thereby causing an epithelial barrier defect, and were subsequently subject to phagocytosis by macrophages.

Conclusions: enters epithelia via an actin-, dynamin-, caveolin-, and Ras-Rac1-dependent endocytosis mechanism and consecutively causes IEC apoptosis primarily in IECs invaded by multiple bacteria. This results in a barrier leak. Moreover, we propose that -packed IECs can be subject to phagocytic uptake by macrophages, thereby opening a potential entry point of into intestinal macrophages.