• Potentiation of epithelial innate host responses by intercellular communication.

      Dolowschiak, Tamas; Chassin, Cécilia; Ben Mkaddem, Sanae; Fuchs, Thilo M; Weiss, Siegfried; Vandewalle, Alain; Hornef, Mathias W; Hannover Medical School, Hannover, Germany. (2010)
      The epithelium efficiently attracts immune cells upon infection despite the low number of pathogenic microbes and moderate levels of secreted chemokines per cell. Here we examined whether horizontal intercellular communication between cells may contribute to a coordinated response of the epithelium. Listeria monocytogenes infection, transfection, and microinjection of individual cells within a polarized intestinal epithelial cell layer were performed and activation was determined at the single cell level by fluorescence microscopy and flow cytometry. Surprisingly, chemokine production after L. monocytogenes infection was primarily observed in non-infected epithelial cells despite invasion-dependent cell activation. Whereas horizontal communication was independent of gap junction formation, cytokine secretion, ion fluxes, or nitric oxide synthesis, NADPH oxidase (Nox) 4-dependent oxygen radical formation was required and sufficient to induce indirect epithelial cell activation. This is the first report to describe epithelial cell-cell communication in response to innate immune activation. Epithelial communication facilitates a coordinated infectious host defence at the very early stage of microbial infection.
    • Tumor invasion of Salmonella enterica serovar Typhimurium is accompanied by strong hemorrhage promoted by TNF-alpha.

      Leschner, Sara; Westphal, Kathrin; Dietrich, Nicole; Viegas, Nuno; Jablonska, Jadwiga; Lyszkiewicz, Marcin; Lienenklaus, Stefan; Falk, Werner; Gekara, Nelson; Loessner, Holger; et al. (2009)
      Several facultative anaerobic bacteria with potential therapeutic abilities are known to preferentially colonize solid tumors after systemic administration. How they efficiently find and invade the tumors is still unclear. However, this is an important issue to be clarified when bacteria should be tailored for application in cancer therapy.