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Humanized Mouse Model to Study Bacterial Infections Targeting the Microvasculature
Published on: April 1, 2014
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.
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.
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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