Role of different Lipid A structures of commensal bacteria in the regulation of colitogenic CD4+ T cell responses

• Applicant: Professorin Dr. Julia-Stefanie Frick
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2011 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 202759103

We demonstrated that the composition of intestinal bacterial communities, more precisely the proportion of Bacteroidetes to Enterobacteriaceae decides on induction of colitis or maintenance of intestinal homeostasis in genetically predisposed hosts. Importantly, Rag1-/- mice that harbor predominantly the anaerobic Bacteroidetes group within their gastrointestinal system are protected from induction of transfer colitis, whereas Rag1-/- mice colonized with a high CFU of Enterobacteriaceae are highly susceptible to intestinal inflammation. Mechanistically, we show that the exchange of laurate by palmitate in the Lipid A of E. coli, and therefore the adjustment of the enterobacterial to the anaerobic Lipid A structure, converts a colitis inducing E. coli strain into a colitis preventing one. Within this project we will define the effects of bacteria expressing different Lipid A structures on activation and maturation of intestinal DC, the T cell activating capacity of dendritic cells primed with different commensal bacteria or Lipid A and colitogenic or non colitogenic T cell responses will be characterized. The project ought to provide a basis as to whether commensal bacteria might prevent or induce inflammatory intestinal diseases and might provide a basis for new preventive or therapeutical strategies in inflammatory bowel diseases (IBD).

• DFG Programme: Research Grants