Neisseria meningitidis-induced sepsis

The aim of this study is to understand the virulence factors behind inflammasome activation, and to get knowledge on the inflammasome-mediated host response mechanisms upon N. meningitidis infection.

 N. meningitidis is a common Gram-negative bacterium localized to the upper respiratory tract but also a major causative agent of sepsis and bacterial meningitis worldwide. The asymptomatic carriers, estimated to be between 5-15 % of the population, are the reservoir for this obligate human pathogen. Due to fast progression of the disease, a meningococcal infection can be fatal within the first 24 hours following dissemination of the bacteria and the death rate of meningococcal disease ranges from 5% in the case of meningitis; up to 40 % in the case of sepsis/septic shock.

• The dramatic onset of meningococcal disease has been suggested to be mainly due to extensive release of endotoxin (lipooligosaccharide, LOS) from the outer membrane the bacterium by triggering host-mediated production of pro-inflammatory cytokine, such as IL-1β, IL-6 and TNF, and our preliminary data suggest that LOS is of crucial importance for caspase-1 activation in neutrophils.