Gene expression and production of tumor necrosis factor alpha, interleukin-1 beta (IL-1 beta), IL-8, macrophage inflammatory protein 1 alpha (MIP-1 alpha), MIP-1 beta, and gamma interferon-inducible protein 10 by human neutrophils stimulated with group B meningococcal outer membrane vesicles

Accumulation of polymorphonuclear neutrophils (PMN) into the subarachnoidal space is one of the hallmarks of Neisseria meningitidis infection. In this study, we evaluated the ability of outer membrane vesicles (OMV) from N. m eningitidis B to stimulate cytokine production by neutrophils. We found tha t PMN stimulated in vitro by OMV produce proinflammatory cytokines and chem okines including tumor necrosis factor alpha (TNF-alpha), interleukin-1 bet a (IL-1 beta), IL-8, macrophage inflammatory protein 1 alpha (MIP-1 alpha), and MIP-1 beta. A considerable induction of gamma interferon (IFN-gamma)-i nducible protein 10 (IP-10) mRNA transcripts, as well as extracellular IP-1 0 release, was also observed when neutrophils were stimulated by OMV in com bination with IFN-gamma. Furthermore, PMN stimulated by OMV in the presence of IFN-gamma demonstrated an enhanced capacity to release TNF-alpha, IL-1 beta, IL-8, and MIP-1 beta compared to stimulation with OMV alone. In line with its down-regulatory effects on neutrophil-derived proinflammatory cyto kines, IL-10 potently inhibited TNF-alpha, IL-1 beta, IL-8, and MIP-1 beta production triggered by OMV. Finally, a neutralizing anti-TNF-alpha monoclo nal antibody (MAb) did not influence the release of IL-8 and MIP-1 beta ind uced by OMV, therefore excluding a role for endogenous TNF-alpha in mediati ng the induction of chemokine release by OMV. In contrast, the ability of l ipopolysaccharide from N. meningitidis B to induce the production of IL-8 a nd MIP-1 beta was significantly inhibited by anti-TNF-alpha MAb. Our result s establish that, in response to OMV, neutrophils produce a proinflammatory profile of cytokines and chemokines which may not only play a role in the pathogenesis of meningitis but may also contribute to the development of pr otective immunity to serogroup B meningococci.