Systemic Inflammatory Response Syndrome (SIRS) is a common condition associated with systemic or severe infections, trauma or haemorrhage. It is characterised by the release of inflammatory cytokines whose main function is to activate the innate and acquired arms of the immune system to fight infection and/or to limit and repair tissue damage. Paradoxically, this enhanced state of responsiveness is followed by a period of immunosuppression that can last for several weeks, long after resolution of the infection or tissue damage that triggered SIRS. The immunosuppressed patients are at risk of suffering secondary or opportunistic infections which are the main cause of mortality and morbidity in critical care patients. Malaria infection can also cause SIRS and immunosuppression, probably contributing to the poor efficacy of vaccination against malaria and other pathogens, and to high incidence of Epstein Barr Virus-induced tumours, in malaria-endemic areas.
We are employing several mouse models to study the effects of SIRS on DC development and function. Pseudoinfection with TLR ligands, or infection with the malaria parasite, induces local changes in the tissues where dendritic cells (DC) develop, leading to continuous formation of paralysed DC with poor antigen presentation function. This effect lasts for several weeks, until the local environment gradually returns to the state pre-SIRS. I will present our characterisation of paralysed DC, the mechanisms that induce them, and strategies to overcome DC paralysis.