Inflammasome-mediated intestinal epithelial defense against pathogens

If you are interested in joining the seminar, please contact: vseminars@mpiib-berlin.mpg.de

Once registered, you will receive a zoom conference link 30 mins before the talk starts - please sign in using your full name.

Talk abstract:

Mammalian barrier tissues such as the intestine or skin are colonized by diverse microbes, living in a state of mutual benefit with the healthy host. However, beneficial bacteria share molecular patterns with pathogens, such as cell wall components or flagella. Thus distinguishing pathogens from commensals and reacting appropriately to infection represents a challenge to the immune system, especially at barrier tissues where both are present. The reaction of an epithelial cell to pathogen assault is often the first decision of the ensuing immune reaction. The inflammasome is an innate immune sensor of pathogenic disturbance of the cytosol and therefore perfectly suited to detect pathogenic behavior, as harmless commensals usually do not access the inside of cells. Studying the NAIP-NLRC4 inflammasome in intestinal epithelial cells (IEC), we observed an important role for this inflammasome, which has previously mostly been studied in immune cells. The coordinated response triggered by IEC inflammasome activation is sufficient to protect against Salmonella tissue invasion and involves IEC expulsion and inflammatory lipid mediator and cytokine production. Excessive inflammasome activation in IECs is sufficient to result in diarrhea and pathology. Using stem cell derived organoids, we show that the surprisingly rapid extrusion response is epithelial cell intrinsic and requires actin rearrangement. Interestingly, the extrusion is not entirely dependent on the canonical inflammasome pathway via Caspase-1 and its downstream cleavage target Gasdermin D.