The in vivo response of the intestinal epithelium to bacterial infection

Final Report Abstract

In vitro studies during the last decades have illustrated the intricate interaction of the enteric pathogen Salmonella (Salmonella Typhimurium) with the intestinal epithelium. However, immortalized cell lines lack final cell differentiation, fail to display the many different epithelial cell types of the gut epithelium and to replicate their interaction and are deprived of environmental signals from the gut lumen such as e.g. the microbiota or the diet and stimuli from the underlying immune cells. We therefore used our recently established neonatal mouse infection model that allows visualization of intraepithelial Salmonella and the analysis of the induced host response. We studied the role of important Salmonella pathogenicity island (SPI)1 and 2 type three secretion system (T3SS) effector molecules during enterocyte invasion, intraepithelial proliferation and cell egress. Also, we analyzed the mucosal response to gut colonization and invasive infection in order to better understand the pathogenesis of Salmonella infection in vivo and identify age-dependent differences in the host-microbial interaction.

Publications

• Identification of a predominantly interferon-λ-induced transcriptional profile in murine intestinal epithelial cells. (2017) Frontiers in Immunology 8(OCT): 1302
  Selvakumar T.A., Bhushal S., Kalinke U., Wirth D., Hauser H., Köster M., Hornef M.W.
  
• Minimal SPI1-T3SS effector requirement for Salmonella enterocyte invasion and intracellular proliferation in vivo. (2018) PLoS Pathogens 14(3): e1006925
  Zhang K., Riba A., Nietschke M., Torow N., Repnik U., Pütz A., Fulde M., Dupont A., Hensel M., Hornef M.W.
  
• Neonatal selection by Tolllike receptor 5 influences long-term gut microbiota composition. (2018) Nature 560(7719): 489-493
  Fulde M., Sommer F., Chassaing B., van Vorst K., Dupont A., Hensel M., Basic M., Klopfleisch R., Rosenstiel P., Bleich A., Bäckhed F., Gewirtz A.T., Hornef M.W.
  
• The olfactory epithelium as a port of entry in neonatal neurolisteriosis. (2018) Nature Communications 9(1): 4269
  Pägelow D., Chhatbar C., Beineke A., Liu X., Nerlich A., van Vorst K., Rohde M., Kalinke U., Förster R., Halle S., Valentin-Weigand P., Hornef M.W., Fulde M.
  
• Bile acids drive the newborn’s gut microbiota maturation. (2020) Nature Communications 11(1): 3692
  van Best N., Rolle-Kampczyk U., Schaap F.G., Basic M., Olde Damink S.W.M., Bleich A., Savelkoul P.H.M., von Bergen M., Penders J., Hornef M.W.
  
• Disturbed gut microbiota and bile homeostasis in Giardia-infected mice contributes to metabolic dysregulation and growth impairment. (2020) Science Translational Medicine 12(565): eaay7019
  Riba A., Hassani K., Walker A., van Best N., von Zeschwitz D., Anslinger T., Sillner N., Rosenhain S., Eibach D., Maiga-Ascofaré O., Rolle-Kampczyk U., Basic M., Binz A., Mocek S., Sodeik B., Bauerfeind R., Mohs A., Trautwein C., Kiessling F., May J., Klingenspor M., Gremse F., Schmitt- Kopplin P., Bleich A., Torow N., von Bergen M., Hornef M.W.
  
• Toward a porcine in vivo model to analyze the pathogenesis of TLR5-dependent enteropathies. (2020) Gut microbes 12(1): 1782163
  Pieper R., van Best N., van Vorst K., Ebner F., Reissmann M., Hornef M.W., Fulde M.
  
• SPI2 T3SS effectors facilitate enterocyte apical to basolateral transmigration of Salmonella-containing vacuoles in vivo. (2021) Gut Microbes 13(1):1973836
  Fulde, M., van Vorst, K., Zhang, K., Westermann, A.J., Busche, T., Huei, Y.C., Welitschanski, K., Froh, I., Pägelow, D., Plendl, J., Pfarrer, C., Kalinowski, J., Vogel, J., Valentin-Weigand, P., Hensel, M., Tedin, K., Repnik, U., Hornef, M.W.