Inflammasomes in Infections and Auto-inflammation
Our research group investigates the function of cytosolic protein complexes termed inflammasomes that play important roles in innate 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. Inflammasomes are involved in numerous inflammatory, metabolic and neurodegenerative diseases, as well as host defense against infections. Our research group focuses on the role of inflammasomes in infections and a number of autoinflammatory diseases that in humans are caused by gain-of-function mutations in genes encoding inflammasome components.
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 signalling
Technology Transfer Potential
- Identification of novel therapeutic targets in managing diseases that are controlled by inflammasome and cell death signaling 2.
- Development of novel genetic mouse models for studying auto-inflammatory diseases
Selected publications
- Eeckhout, E. et al. Gasdermin D independent canonical inflammasome responses cooperate with caspase-8 to establish host defense against gastrointestinal Citrobacter rodentium infection. Cell Death Dis 14, 282 (2023). Visit ➚
- Jorch, S. K. et al. Complex regulation of alarmins S100A8/A9 and secretion via gasdermin D pores exacerbates autoinflammation in familial Mediterranean fever. J Allergy Clin Immunol 152, 230-243 (2023). Visit ➚
- Frising, U. C. et al. Nlrp3 inflammasome activation in macrophages suffices for inducing autoinflammation in mice. EMBO Rep, e54339 (2022). Visit ➚
- Dubois, H. et al. Nlrp3 inflammasome activation and Gasdermin D-driven pyroptosis are immunopathogenic upon gastrointestinal norovirus infection. PLoS pathogens 15, e1007709 (2019). Visit ➚
- Mamantopoulos, M. et al. Nlrp6- and ASC-Dependent Inflammasomes Do Not Shape the Commensal Gut Microbiota Composition. Immunity 47, 339-348 (2017). Visit ➚
Bibliography
- Full bibliography Visit ➚
Immunostaining for activated inflammasomes (red dots) in LPS/ATP-treated primary mouse macrophages.