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Isolation of Mouse Lung Dendritic Cells
Published on: November 22, 2011
Innate Immune Sensing of Fusarium culmorum by Mouse Dendritic Cells
Gaëlle Vacher1, Eleonora Ciarlo, Dessislava Savova-Bianchi
1a Service of Occupational Hygiene , Institute for Work and Health, University of Lausanne and Geneva , Epalinges-Lausanne , Switzerland.
Abstract:
Chronic inhalation of grain dust is associated with asthma and chronic bronchitis in grain worker populations. Exposure to fungal particles was postulated to be an important etiologic agent of these pathologies. Fusarium species frequently colonize grain and straw and produce a wide array of mycotoxins that impact human health, necessitating an evaluation of risk exposure by inhalation of Fusarium and its consequences on immune responses. Data showed that Fusarium culmorum is a frequent constituent of aerosols sampled during wheat harvesting in the Vaud region of Switzerland. The aim of this study was to examine cytokine/chemokine responses and innate immune sensing of F. culmorum in bone-marrow-derived dendritic cells and macrophages. Overall, dendritic cells and macrophages responded to F. culmorum spores but not to its secreted components (i.e., mycotoxins) by releasing large amounts of macrophage inflammatory protein (MIP)-1α, MIP-1β, MIP-2, monocyte chemoattractant protein (MCP)-1, RANTES, and interleukin (IL)-12p40, intermediate amounts of tumor necrosis factor (TNF), IL-6, IL-12p70, IL-33, granulocyte colony-stimulating factor (G-CSF), and interferon gamma-induced protein (IP-10), but no detectable amounts of IL-4 and IL-10, a pattern of mediators compatible with generation of Th1 or Th17 antifungal protective immune responses rather than with Th2-dependent allergic responses. The sensing of F. culmorum spores by dendritic cells required dectin-1, the main pattern recognition receptor involved in β-glucans detection, but likely not MyD88 and TRIF-dependent Toll-like receptors. Taken together, our results indicate that F. culmorum stimulates potently innate immune cells in a dectin-1-dependent manner, suggesting that inhalation of F. culmorum from grain dust may promote immune-related airway diseases in exposed worker populations.
Insights
Inhaling Fusarium culmorum spores from grain dust activates innate immune cells, potentially contributing to grain worker asthma and bronchitis. This immune response is dectin-1 dependent, not allergic.
Area of Science:
- Immunology
- Occupational Health
- Mycology
Background:
- Chronic grain dust exposure is linked to asthma and bronchitis in workers.
- Fungal particles, particularly Fusarium species, are suspected etiological agents.
- Fusarium species produce mycotoxins impacting human health.
Purpose of the Study:
- To investigate immune responses to Fusarium culmorum in immune cells.
- To determine the role of innate immune sensing pathways in response to F. culmorum.
Main Methods:
- Bone marrow-derived dendritic cells and macrophages were exposed to F. culmorum spores and secreted components.
- Cytokine and chemokine release was measured.
- Immune sensing pathways, including dectin-1 and Toll-like receptors (TLRs), were investigated.
Main Results:
- Immune cells released significant inflammatory mediators (MIP-1α, MCP-1, IL-12p40) in response to F. culmorum spores, but not mycotoxins.
- Responses included mediators associated with Th1/Th17 responses, not Th2-allergic responses.
- Sensing of F. culmorum spores by dendritic cells was dectin-1 dependent and likely independent of MyD88/TRIF-dependent TLRs.
Conclusions:
- Fusarium culmorum spores potently stimulate innate immune cells via dectin-1.
- This immune activation pattern suggests a role in promoting immune-related airway diseases in grain workers.
- Inhalation of F. culmorum may contribute to occupational respiratory pathologies.
