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Title (Primary) Exposure to mycotoxins increases the allergic immune response in a murine asthma model
Author Schütze, N.; Lehmann, I.; Bönisch, U.; Simon, J.-C.; Polte, T.;
Journal American Journal of Respiratory and Critical Care Medicine
Year 2010
Department IMMU;
Volume 181
Issue 11
Language englisch;
Keywords air pollution; allergy; dendritic cells; Th1/Th2 cells
Abstract Rationale: Epidemiological studies have shown that indoor molds are associated with increased prevalence and exacerbation of respiratory symptoms and asthma. Mycotoxins, secondary metabolites of molds, may contribute to these effects. Objectives: To investigate the adjuvant activity of mycotoxins on allergic airway inflammation. Methods: Balb/c mice were exposed via the airways to gliotoxin and via the intestine to patulin, sensitized with ovalbumin (OVA), and then analyzed in acute and chronic murine asthma models. In addition, the effect of mycotoxin exposure on dendritic cell (DC) function was investigated using murine bone marrow-derived DCs. Measurements and Main Results: Exposure of mice to both mycotoxins enhanced dose-dependently airway hyperreactivity, eosinophilic lung inflammation, and OVA-specific IgE serum levels compared with mice that received only the antigen. These findings correlated with increased Th2 cytokine levels and decreased IFN- production. Long-term mycotoxin exposure exacerbated chronic airway inflammation and airway remodeling. In vitro or in vivo mycotoxin exposure inhibited IL-12 production in maturing DCs and enhanced airway inflammation after adoptive DC transfer into Balb/c mice. Mycotoxin exposure enhanced OVA-induced lung lipid peroxidation and moderately increased isoprostane levels in naive mice. Treatment of mycotoxin-exposed DCs with the antioxidants N-acetylcysteine or glutathione ethyl ester restored IL-12 secretion and pretreatment of exposed mice with N-acetylcysteine prevented the mycotoxin-induced increase of airway inflammation and AHR. Conclusions: Our results demonstrate that gliotoxin and patulin increase the allergic immune response in mice by modulating the Th1/Th2 balance via direct effects on IL-12 secretion in DCs and by inducing oxidative stress.
ID 10501
Persistent UFZ Identifier http://www.ufz.de/index.php?en=20939&ufzPublicationIdentifier=10501
Schütze, N., Lehmann, I., Bönisch, U., Simon, J.-C., Polte, T. (2010):
Exposure to mycotoxins increases the allergic immune response in a murine asthma model
Am. J. Respir. Crit. Care Med. 181 (11), 1188 - 1199