Our research group investigates the function of cytosolic protein complexes termed inflammasomes that play important roles in immune responses. Inflammasome activation happens through a sensor protein that senses the trigger, after which a protease termed caspase-1 executes inflammasome functions. Both pathogens and host-derived danger and stress signals can trigger caspase-1 activity of inflammasomes, which then cleave their substrates. These substrates include Gasdermin D, of which the N-terminal fragment triggers a lytic form of cell death termed pyroptosis. This inflammasome-induced cell death mode is accompanied by the release of the IL-1β and IL-18 pro-inflammatory cytokines, both of which are maturated by caspase-1 activity, as well as several danger-associated molecular patterns that together mount an efficient inflammatory response.
Areas of expertise
- Genetic mouse models of rare human auto-inflammatory diseases caused by gain-of-function mutants of inflammasome signaling proteins
- In vivo and ex vivo models of bacterial, viral and fungal infectious diseases
- In vivo humanized mouse models and ex vivo primary human cell models
- In vivo and primary cell ex vivo analysis of inflammasome and cell death signaling
Technology transfer potential
- Identification of novel therapeutic targets in managing diseases that are controlled by inflammasome and cell death signaling
- Development of novel genetic mouse models for studying auto-inflammatory diseases
- Mamantopoulos, M., Ronchi, F et al. Nlrp6- and ASC-Dependent Inflammasomes Do Not Shape the Commensal Gut Microbiota Composition.
Immunity. 47, 339-348, 2017.
- Dubois H et al. Nlrp3 inflammasome activation and Gasdermin D-driven pyroptosis are immunopathogenic upon gastrointestinal norovirus infection.
PLoS Pathog, 15, e1007709, 2019.
- Rogiers et al. Candidalysin crucially contributes to Nlrp3 inflammasome activation by Candida albicans hyphae.
mBio 2019, 10 (1): e02221-18.
- Mamantopoulos et al. El Tor biotype Vibrio cholerae activates the caspase-11-independent canonical Nlrp3 and Pyrin inflammasomes.
Frontiers in Immunology 2019, 10, 2463.
- De Schutter et al. Punching Holes in Cellular Membranes: Biology and Evolution of Gasdermins.
Trends in Cell Biology 2021, S0962-8924(21)00050-7.
Histology and endoscopy of colitis in mice
Phylogenetic 16S DNA microbiota profiling
Intestinal epithelial organoid live cell imaging