Deoxynivalenol and Satratoxin G Potentiate Proinflammatory Cytokine and Macrophage Inhibitory Protein 2 Induction by Listeria and Salmonella in the Macrophage

Abstract

Health risks from microbial pathogens and toxins encountered in food and the environment continue to be of worldwide concern. The purpose of this research was to test the hypothesis that trichothecene mycotoxins amplify inflammatory responses to foodborne bacterial pathogens. We assessed the capacity of deoxynivalenol (DON) and satratoxin G (SG) to potentiate chemokine and proinflammatory cytokine production in RAW 264.7 murine macrophages induced by Listeria monocytogenes and Salmonella Typhimurium. When macrophage cultures were incubated with killed irradiated suspensions of the pathogens for 24 h, the minimum Listeria concentrations for induction of macrophage inhibitory protein 2 (MIP-2), interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α) were 0.01, 0.01, 1.0, and 1.0 μg/ml (P <0.05) and the minimum Salmonella concentrations were 0.01, 0.01, 0.1, and 0.1 μg/ml, respectively (P <0.05). Induction of all four mediators by both pathogens was potentiated by DON (at 100 and 250 ng/ml); observed responses were significantly higher than predicted additive responses (P <0.05). SG (at 2 and 5 ng/ml) also significantly amplified induction of IL-1β and TNF-α (P <0.05) by both Listeria and Salmonella. These results indicate that DON encountered in Fusarium-contaminated food and SG from Stachybotrys-contaminated indoor environments could magnify innate inflammatory responses to foodborne bacterial pathogens.