Innate Immune Sensing of Fusarium culmorum by Mouse Dendritic Cells.

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-1ß, 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 ß-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.

Frequent Occupational Exposure to Fusarium Mycotoxins of Workers in the Swiss Grain Industry.

Type B trichotecens such as deoxynivalenol (DON), 3-acetyldeoxynivalenol (3-ADON), 15-acetyldeoxynivalenol (15-ADON), nivalenol (NIV) and zearalenone (ZEN) are mycotoxins contaminating wheat and wheat dust. Mycotoxins are toxic upon ingestion and considered potentially toxic when inhaled. Whereas dietary exposure to mycotoxins is controlled in food, data on occupational exposure by inhalation by grain workers are scarce. The objectives of this study were to determine the incidence of DON, 3-ADON, 15-ADON, NIV and ZEN in aerosols generated during grain harvesting and unloading and the risk of exposure of grain workers. Aerosols were collected during the threshing of 78 winter wheat fields and grain unloading of 59 grain lots in six grain terminals in the Vaud region (Switzerland). The samples represented the diversity of the winter wheat cultivar and of the farming system (88 treated with fungicides, 46 untreated). Using a HPLC MS/MS method developed to quantify mycotoxins in aerosols, we report that the mycotoxin content of aerosols was not affected by the wheat cultivars or farming system, but that the incidence of the mycotoxins differed between activities. While wheat harvesting generated on average 28, 20 and 1 ng·m-3 of DON, NIV and ZEN, respectively, grain unloading generated 53, 46 and 4 ng·m-3. Personal sampling revealed that working in a cab was an efficient protective measure. However, it was not sufficient to avoid chronic exposure to multiple mycotoxins. The most exposed activity was the cleaning, exposing workers to DON, NIV and ZEN at concentrations as high as 65, 59 and 3 ng·m-3. These data provide valuable information for future studies of mycotoxin toxicity at relevant concentrations on respiratory health.