Interaction of Neisseria meningitidis with human dendritic cells

Infection with Neisseria meningitidis serogroup B is responsible for fatal septicemia and meningococcal meningitis. The severity of disease directly c orrelates with the production of the proinflammatory cytokines tumor necros is factor alpha (TNF-alpha), interleukin-1 (IL-1), IL-6, and IL-8. However, the source of these cytokines has not been clearly defined yet. Since bact erial infection involves the activation of dendritic cells (DCs), we analyz ed the interaction of N. meningitidis with monocyte-derived DCs. Using N. m eningitidis serogroup B wild-type and unencapsulated bacteria, we found tha t capsule expression significantly impaired neisserial adherence to DCs. In addition, phagocytic killing of the bacteria in the phagosome is reduced b y at least 10- to 100-fold. However, all strains induced strong secretion o f proinflammatory cytokines TNF-alpha., IL-6, and IL-8 by DCs (at least 1,0 00-fold at 20 h postinfection [p.i]), with significantly increased cytokine levels being measurable by as early as 6 h p.i. Levels of IL-1 beta, in co ntrast, were increased only 200- to 400-fold at 20 h p.i. with barely measu rable induction at 6 h p.i. Moreover, comparable amounts of cytokines were induced by bacterium-free supernatants of Neisseria cultures containing nei sserial lipooligosaccharide as the main factor. Our data suggest that activ ated DCs may be a significant source of high levels of proinflammatory cyto kines in neisserial infection and thereby may contribute to the pathology o f meningococcal disease.