Lactobacillus plantarum extracellular vesicles inhibit avian reovirus replication via activation of the STING-IRF3 signaling pathway

Avian reovirus (ARV) poses a severe threat to the poultry industry owing to its immunosuppressive properties. Although current vaccine strategies have achieved certain efficacy, they still face challenges such as strain mismatch and immunosuppressive. Extracellular vesicles produced by probiotics, for instance those from Lactobacillus plantarum (Lp), are critically involved in modulating immune responses against bacterial and viral infections. However, the underlying molecular mechanisms remain unclear. This study demonstrated that Lactobacillus plantarum extracellular vesicles (LpEVs) could inhibit ARV replication in DF-1 (chicken embryo fibroblast) cells. We further demonstrated that treatment with LpEVs could promote the phosphorylation of STING (p-STING) and IRF3 (p-IRF3), leading to a significant up-regulation in the secretion of IFN-β and the transcription of interferon-stimulated genes (ISGs). Moreover, these changes primarily depended on STING, as its anti-ARV activity was significantly attenuated following treatment with STING siRNA. We also observed that LpEVs significantly alleviated damage induced by ARV in goslings, as evidenced by the lower rate of body weight loss, reduced viral shedding, and attenuated inflammatory responses in the tissue. Consistently, a significant activation of the STING-IRF3 pathway and an increase in IFN-β secretion were observed. In conclusion, LpEVs demonstrate anti-ARV activity by activating STING-mediated innate immunity, underscoring their considerable potential as novel antiviral postbiotics. This study lays a theoretical foundation for the development of new strategies for ARV prevention and control.