Hypervirulent MenB causing fatal human infections frequently display the 
oligomeric-coiled coil adhesin NadA, a 45-kDa intrinsic outer membrane protein 
implicated in binding to and invasion of respiratory epithelial cells. A 
recombinant soluble mutant lacking the 10-kDa COOH terminal membrane domain 
(NadA(Delta351-405)) also activates human monocytes/macrophages/DCs. As NadA is 
physiologically released during sepsis as part of OMVs, in this study, we tested 
the hypothesis that NadA(+) OMVs have an enhanced or modified 
proinflammatory/proimmune action compared with NadA(-) OMVs. To do this we 
investigated the activity of purified free NadA(Delta351-405) and of OMVs from 
MenB and Escherichia coli strains, expressing or not full-length NadA. 
NadA(Delta351-405) stimulated monocytes and macrophages to secrete cytokines 
(IL-1beta, TNF-alpha, IL-6, IL-12p40, IL-12p70, IL-10) and chemokines (IL-8, 
MIP-1alpha, MCP-1, RANTES), and full-length NadA improved MenB OMV activity, 
preferentially on macrophages, and only increased cytokine release. 
NadA(Delta351-405) induced the lymphocyte costimulant CD80 in monocytes and 
macrophages, and NadA(+) OMVs induced a wider set of molecules supporting 
antigen presentation (CD80, CD86, HLA-DR, and ICAM-1) more efficiently than 
NadA(-) OMVs only in macrophages. Moreover, membrane NadA effects, unlike 
NadA(Delta351-405) ones, were much less IFN-gamma-sensitive. The activity of 
NadA-positive E. coli OMVs was similar to that of control OMVs. NadA in MenB 
OMVs acted at adhesin concentrations approximately 10(6) times lower than those 
required to stimulate cells with free NadA(Delta351-405).