Neutrophils undergo migration and produce an antiviral response following porcine epidemic diarrhea virus infection

The importance of the host's initial innate immune and acute inflammatory responses in combating viral infections has increasingly garnered interest. Neutrophils are the initial responders to infection and inflammation; however, their specific function in the host's antiviral immune defence remains ambiguous. Here, we observed that the porcine epidemic diarrhea virus (PEDV), which is the primary pathogen responsible for diarrhea in newborn piglets, triggered the release of intestinal neutrophil-attracting chemokines, recruiting neutrophils to the intestinal epithelium and inducing an antiviral response. In the co-culture model of Vero cells (a cell line used to study the replication and dynamics of PEDV in vitro) and neutrophils, infection of Vero cells with PEDV facilitated the transepithelial migration of neutrophils. Additionally, direct contact between neutrophils and PEDV-infected Vero cells enhanced viral clearance. Transcriptome analysis revealed significant upregulation of C3 expression in Vero cells after neutrophils were introduced 6 h after PEDV infection, and the antiviral effect of neutrophils was diminished after siRNA-mediated knockdown of C3. Consistently, C3 expression was markedly upregulated in the small intestine of PEDV-infected piglets, supporting complement system activation. Furthermore, the supernatant from cells infected with PEDV has the capacity to increase the expression of antiviral agents such as β-defensin-2 and myeloperoxidase in neutrophils. Taken together, our results reveal the role of neutrophil recruitment in the antiviral response during enterovirus infection, highlighting the importance of neutrophilic activity in the host antiviral innate immune response.