Journal
JOURNAL OF LEUKOCYTE BIOLOGY
Volume 83, Issue 5, Pages 1100-1110Publisher
FEDERATION AMER SOC EXP BIOL
DOI: 10.1189/jlb.1207810
Keywords
adhesion molecule; bacterial infection; inflammation; cytokines; chemokines
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Specific surface proteins of Neisseria meningitidis have been proposed to stimulate leukocytes during tissue invasion and septic shock. In this study, we demonstrate that the adhesin N. meningitidis Adhesin A (NadA) involved in the colonization of the respiratory epithelium by hypervirulent N. meningitidis B strains also binds to and activates human monocytes/macrophages. Expression of NadA on the surface on Escherichia coli does not increase bacterial-monocyte association, but a NadA-positive strain induced a significantly higher amount of TNF-alpha and IL-8 compared with the parental NadA-negative strain, suggesting that NadA has an intrinsic stimulatory action on these cells. Consistently, highly pure, soluble NadA(Delta 351-405), a proposed component of an antimeningococcal vaccine, efficiently stimulates monocytes/macrophages to secrete a selected pattern of cytokines and chemotactic factors characterized by high levels of IL-8, IL-6, MCP-1, and MIP-1 alpha and low levels of the main vasoactive mediators TNF-alpha and IL-1. NadA(Delta 351-405) also inhibited monocyte apoptosis and determined its differentiation into a macrophage-like phenotype.
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