Two-way immune effects of deoxynivalenol in weaned piglets and porcine alveolar macrophages: Due mainly to its exposure dosage

Mycotoxins are toxic metabolites produced by fungal species that occur frequently in cereals and animal forages throughout the world, posing a serious threat to humans and animals. Although some studies showed the immunotoxicity of mycotoxins, little research focused on the two-way effects of mycotoxins on immune response in vitro and vivo. Here, we explored the effects of deoxynivalenol (DON), one of the most widely distributed mycotoxins, on immune function of piglets and porcine alveolar macrophages (PAMs), and found it exhibited bidirectional immune effects due to different exposure doses. Our results revealed that low doses of DON increased the expressions of TNF-α and IL-6 in piglets and PAMs, promoted the chemotaxis and phagocytosis of PAMs and transformed macrophages to M1 phenotype (P < 0.05). Conversely, high doses of DON increased the expressions of TGF-β and IL-10 in piglets and PAMs, inhibited the chemotaxis and phagocytosis of PAMs and induced macrophages M2-type polarization (P < 0.05). Mechanistically, DON exposure significantly activated the TLR4/NFκB pathway at low doses and induced mitophagy-mediated mitochondrial dysfunction at high doses in vitro and vivo. TLR4 interference and mitophagy activator, CCCP, were used to further confirm their roles. Therefore, we concluded that DON exposure at low doses caused immunostimulation via activating TLR4/NFκB, whereas it was immunoinhibitory at high doses through blocking mitophagy. Our study suggested that both high and low doses mycotoxins contamination might be harmful, and further back up the necessity to take a vigilant attitude to minimize humans and animals intake of mycotoxins in the environment.