About this team
The incidences of sepsis and septic shock, which may develop as severe manifestations of bacteraemia, has increased significantly over the last two decades and continue to be a major cause of morbidity and mortality worldwide. IL-1β is one of the major cytokines produced during sepsis but despite this proinflammatory involvement, the innate immune system in septic patients is suppressed and unable to clear pathogens. The excessive cytokine levels seem rather to stage for tissue injury and organ failure than protection, and high levels of IL-1β correlates with severity and mortality. Caspase-1 (and/or caspase-11) has been suggested as guardians against severe infections and sepsis. Despite the knowledge that much of the damage inflicted in the septic host is attributable to the host’s own response to microbial virulence factors, data regarding the host innate immune response towards bacteria, as well as the molecular mechanisms linking caspase-1 activation to development of severe inflammation and sepsis, is currently lacking. To be able to effectively and efficiently care for these patients, it is crucial to understand WHEN and HOW sepsis progress from hyper to hypo-inflammation.
Our research aims to understand the innate immune host response mechanisms during the disease course of sepsis caused by S. aureus, E. coli and Neisseria meningitidis. The focus is set on the role of the inflammasome and the interplay between caspase-1 and IL-1β.