Intestinal epithelial NAIP/NLRC4 function in infection

This research project aims to better understand how our immune system is able to detect infections in the gastrointestinal tract. The intestine is filled with useful microbial flora that is tolerated and not attacked by the immune system, despite the fact that disease causing and harmless gut bacteria (commensals) are generally very similar in their structures. We hypothesize, that not only immune cells but also epithelial cells lining the intestine can detect disease-causing bacteria using a detection system called the NAIP/NLRC4 inflammasome. This detection system allows cells to react to bacteria that have entered their inside, a behavior that usually does not occur in harmless commensal bacteria but is very common among infectious bacteria like Salmonella. To prove this hypothesis, we use new mouse models that can only detect bacterial structures inside their intestinal epithelial cells but not in their immune cells, or that lack the ability to detect certain bacterial structures inside all of their cells. We will study two models of infection: Salmonella, which can be the cause of severe food poisoning and typhoid fever, and Citrobacter rodentium, which is a mouse model of enteropathogenic/ enterohaemorrhagic E. coli (EPEC/EHEC), which cause bloody diarrhea, that can be deadly, especially in infants. These novel models will help us understand how the immune system detects gastrointestinal pathogens, which is crucial for our deeper insight into general immune processes sites as well as to develop therapies for infections with these pathogens.

No additional funding sources recorded.