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Hemoglobin and Streptococcus suis cell wall act in synergy to potentiate the inflammatory response of
Shin-Ichi Tanabe1, Marcelo Gottschalk, Daniel Grenier
1Groupe de Recherche en Ecologie Buccale, Faculté de Médecine Dentaire, Université Laval, Quebec City, Quebec, Canada.
Abstract:
Streptococcus suis, a major swine pathogen world-wide, can trigger macrophages to secrete large amounts of proinflammatory cytokines, which increase the permeability of the blood-brain barrier. In this study, we hypothesized that hemoglobin may potentiate the inflammatory response of human macrophages stimulated with a S. suis cell-wall preparation. Monocyte-derived macrophages were stimulated with the S. suis cell-wall preparation in the presence or absence of human hemoglobin, and the secretion of interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), IL-6, and IL-8 was analyzed by enzyme-linked immunosorbent assays. The cell-wall preparation induced dose-dependent IL-1beta, TNF-alpha, IL-6, and IL-8 responses in macrophages. Hemoglobin potentiated the cell-wall induced inflammatory response, resulting in a significantly higher secretion of all the cytokines. The S. suis cell-wall preparation in combination with hemoglobin activated macrophage intracellular kinases involved in inflammatory signaling pathways. In conclusion, hemoglobin, which may be released in vivo by the action of S. suis suilysin on red blood cells, contributes to raising the levels of pro-inflammatory mediators by acting in synergy with S. suis cell-wall components. This phenomenon may contribute to the development and the severity of meningitis.
Insights
This study shows that hemoglobin amplifies the inflammatory response in human macrophages when exposed to Streptococcus suis cell walls. This synergy may worsen meningitis severity.
Area of Science:
- Immunology
- Microbiology
- Pathogenesis
Background:
- Streptococcus suis is a significant global swine pathogen.
- S. suis can induce macrophages to release pro-inflammatory cytokines, increasing blood-brain barrier permeability.
- The role of hemoglobin in S. suis-induced inflammation was previously unclear.
Purpose of the Study:
- To investigate if hemoglobin potentiates the inflammatory response of human macrophages stimulated by S. suis cell-wall preparations.
- To elucidate the mechanisms underlying this potentiation.
Main Methods:
- Human monocyte-derived macrophages were stimulated with S. suis cell-wall preparations.
- The presence or absence of human hemoglobin was varied.
- Cytokine secretion (IL-1beta, TNF-alpha, IL-6, IL-8) was measured using enzyme-linked immunosorbent assays.
- Macrophage intracellular kinase activation was assessed.
Main Results:
- S. suis cell-wall preparation induced a dose-dependent release of IL-1beta, TNF-alpha, IL-6, and IL-8.
- Hemoglobin significantly potentiated the cell-wall induced inflammatory response, increasing all cytokine secretions.
- Combined S. suis cell-wall and hemoglobin treatment activated macrophage intracellular kinases involved in inflammatory signaling.
Conclusions:
- Hemoglobin synergizes with S. suis cell-wall components to enhance the secretion of pro-inflammatory mediators.
- This synergistic effect, potentially involving hemoglobin released by S. suis suilysin, may contribute to the development and severity of meningitis.
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