Uptake of Tropheryma whipplei by Intestinal Epithelia

Julian Friebel, Katina Schinnerling, Kathleen Weigt, Claudia Heldt, Anja Fromm, Christian Bojarski, Britta Siegmund, Hans Jörg Epple, Judith Kikhney, Annette Moter, Thomas Schneider, Jörg D. Schulzke, Verena Moos, Michael Schumann

Research output: Contribution to journalArticlepeer-review


Background: Tropheryma whipplei (TW) 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 TW-induced gastroenteritis are currently unknown. Methods: Using ex vivo disease models comprising human duodenal mucosa exposed to TW in Ussing chambers, various intestinal epithelial cell (IEC) cultures exposed to TW and a macrophage/IEC coculture model served to characterize endocytic uptake mechanisms and barrier function. Results: TW exposed ex vivo to human small intestinal mucosae is capable of autonomously entering IECs, thereby invading the mucosa. Using dominant-negative mutants, TW 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. TW-invaded IECs underwent apoptosis, thereby causing an epithelial barrier defect, and were subsequently subject to phagocytosis by macrophages. Conclusions: TW enters epithelia via an actin-, dynamin-, caveolin-, and Ras-Rac1-dependent endocytosis mechanism and consecutively causes IEC apoptosis primarily in IECs invaded by multiple TW bacteria. This results in a barrier leak. Moreover, we propose that TW-packed IECs can be subject to phagocytic uptake by macrophages, thereby opening a potential entry point of TW into intestinal macrophages.

Original languageEnglish
Article number6197
JournalInternational Journal of Molecular Sciences
Issue number7
Publication statusPublished - Apr 2023


  • apoptosis
  • barrier function
  • caveolin
  • endocytosis
  • gastroenteritis
  • invasion
  • Tropheryma whipplei
  • Ussing chamber
  • Whipple’s disease

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry


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