Deoxynivalenol aggravates the immunosuppression in piglets and PAMs under the condition of PEDV infection through inhibiting TLR4/NLRP3 signaling pathway

Mycotoxins are toxic metabolites produced by fungi, which are ubiquitous in cereals and feed worldwide and threaten human and animal health. Deoxynivalenol (DON) is one of the most prevalent mycotoxins and causes a series of toxicities, especially enterotoxicity and immunotoxicity. Porcine epidemic diarrhea virus (PEDV) is a destructive enteropathogenic animal coronavirus, is often accompanied with DON contamination in the swine herd. Previous studies have shown that PEDV infection leads severe immunosuppression in pigs. However, whether DON exposure aggravates the PEDV-induced immunosuppression remains unclear. In this study, weaned piglet and porcine alveolar macrophage cell (PAM) models were established to explore the effects of DON on the PEDV-induced immunosuppression and to clarify its underlying mechanism. The in vivo results showed that 2.25 mg/kg feed DON significantly exacerbated the immunosuppressive effects on the PEDV-infected piglets, as demonstrated by the decreases in growth performance, the numbers of goblet cells and CD3+T cells, as well as the protein expressions of ZO-1, Claudin1 and Muc2, in addition to the increases in anti-inflammatory factors levels and the intestinal injury. Similarly, the in vitro results demonstrated that 3-4 μM DON markedly aggravated apoptosis, enhanced the expressions of anti-inflammatory factors, but reduced the migration and phagocytosis abilities of the PEDV-infected PAMs. Furthermore, DON significantly suppressed the expressions of TLR4/NLRP3 in vivo and in vitro. To contrast, lipopolysaccharide (LPS), the corresponding activator, obviously alleviated the DON-exacerbated immunosuppression. Our findings suggest that DON could aggravate host immunosuppression under the condition of PEDV infection through inhibiting TLR4/NLRP3 signaling pathway, and provide novel theoretical insights into the further studies on the immunotoxicity of DON contamination and PEDV-induced immunosuppression.