Human monocytes/macrophages are a target of Neisseria meningitidis Adhesin A (NadA)

Susanna Franzoso1, Cristina Mazzon, Maryta Sztukowska

  • 1Centro Ricerche Biotecnologie Innovative, Università di Padova, Padova, Italy.

Insights

Neisseria meningitidis adhesin A (NadA) activates human immune cells, stimulating cytokine release and preventing cell death. This suggests NadA plays a key role in meningococcal pathogenesis and immune response.

Area of Science:

  • Immunology
  • Microbiology
  • Molecular Biology

Background:

  • Neisseria meningitidis surface proteins are implicated in leukocyte stimulation during invasive disease.
  • The adhesin N. meningitidis Adhesin A (NadA) is crucial for respiratory epithelium colonization by virulent strains.

Purpose of the Study:

  • To investigate the role of NadA in human monocyte/macrophage activation.
  • To determine if NadA directly stimulates immune cells independently of bacterial adhesion.

Main Methods:

  • Surface expression of NadA on Escherichia coli to assess bacterial-monocyte interactions.
  • Stimulation of human monocytes/macrophages with purified soluble NadA(Delta351-405).
  • Measurement of cytokine and chemokine secretion, monocyte apoptosis, and differentiation.

Main Results:

  • NadA-expressing E. coli induced higher TNF-alpha and IL-8 compared to NadA-negative strains.
  • Purified soluble NadA(Delta351-405) stimulated monocytes/macrophages to secrete IL-8, IL-6, MCP-1, and MIP-1alpha.
  • NadA(Delta351-405) inhibited monocyte apoptosis and promoted differentiation into a macrophage-like phenotype.

Conclusions:

  • NadA possesses intrinsic immune-stimulatory properties, activating monocytes/macrophages.
  • NadA influences immune responses by modulating cytokine profiles and affecting monocyte survival and differentiation.
  • These findings highlight NadA's significance in meningococcal pathogenesis and potential as a vaccine component.

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