Secreted proteins from Neisseria meningitidis mediate differential human gene expression and immune activation

Summary Meningococcal secreted proteins (MSPs) have been poorly characterized. We hypothesized that MSPs play essential roles in host–bacterial interactions and in the pathogenesis of disease. In order to test this, we examined differential host gene expression in human meningeal‐derived cells, in response to endotoxin‐depleted MSPs compared to live bacteria. Using expression arrays, upregulated expression of several pro‐inflammatory and apoptosis‐related genes was found to be induced by MSPs. The transcription and translation of representative genes was confirmed by using various methods. Increased interleukin 8 (IL‐8) and cyclooxygenase 2 (COX‐2) gene transcription was confirmed using real‐time PCR. Upregulated IL‐8, IL‐6, ICAM‐1 and COX‐2 protein expression were confirmed by ELISA, flow cytometry or Western immunoblots. Furthermore, exposure of cells to MSPs or live meningococci induced a small significant resistance effect to staurosporine‐induced apoptosis. Secreted meningococcal virulence factors are therefore important in inducing host inflammatory responses and resistance to apoptosis, and they are worthy of extensive investigation.