title: Human monocytes/macrophages are a target of Neisseria meningitidis Adhesin A (NadA).
abstract: 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(Delta351-405), 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-1alpha and low levels of the main vasoactive mediators TNF-alpha and IL-1. NadA(Delta351-405) also inhibited monocyte apoptosis and determined its differentiation into a macrophage-like phenotype.
authors.affiliation: Centro Ricerche Biotecnologie Innovative, Università di Padova, Padova, Italy.
authors.forename: Susanna
authors.initials: S
authors.lastname: Franzoso
authors.forename: Cristina
authors.initials: C
authors.lastname: Mazzon
authors.forename: Maryta
authors.initials: M
authors.lastname: Sztukowska
authors.forename: Paola
authors.initials: P
authors.lastname: Cecchini
authors.forename: Tihana
authors.initials: T
authors.lastname: Kasic
authors.forename: Barbara
authors.initials: B
authors.lastname: Capecchi
authors.forename: Regina
authors.initials: R
authors.lastname: Tavano
authors.forename: Emanuele
authors.initials: E
authors.lastname: Papini
mesh_terms: D018829:Adhesins, Bacterial / Q000235:genetics / Q000502:physiology*; D004847:Epithelial Cells / Q000382:microbiology; D004926:Escherichia coli / Q000235:genetics / Q000472:pathogenicity; D006367:HeLa Cells / Q000382:microbiology; D006801:Humans; D016209:Interleukin-8 / Q000097:blood; D007962:Leukocytes / Q000382:microbiology* / Q000502:physiology; D008264:Macrophages / Q000382:microbiology*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009000:Monocytes / Q000382:microbiology*; D009345:Neisseria meningitidis / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014774:Virulence
chemical_list: D018829:Adhesins, Bacterial; D016209:Interleukin-8; C501982:NadA protein, Neisseria meningitidis; D014409:Tumor Necrosis Factor-alpha