Lactiplantibacillus plantarum GUANKE Enhances Antiviral Defense Against Respiratory Syncytial Virus Through the STING-TBK1-IRF3-IFN Pathway

<b>Background/Objectives:</b> To investigate the antagonistic effect of probiotic <i>Lactiplantibacillus plantarum</i> GUANKE against respiratory syncytial virus (RSV) and its underlying molecular mechanisms. <b>Methods:</b> in vitro cell models (A549 and HEp2 cells) and an in vivo mouse model (BALB/c mice) were employed. RT-qPCR, TCID50 assay, immunofluorescence, ELISA, Western blot, and histopathological analysis were used to investigate the effects of GUANKE on RSV replication, inflammatory responses, and the type I interferon pathway. <b>Results:</b> Oral administration of GUANKE effectively cleared RSV and alleviated RSV-induced pulmonary inflammatory responses. GUANKE inhibited viral replication. The GUANKE intervention group exhibited significantly reduced pathological damage to lung tissue and decreased the expression of inflammatory cytokines (IL-1β, IL-6, MCP-1, TNF-α). GUANKE augmented the early type I interferon response and activated the STING-TBK1-IRF3-IFN signaling pathway. <b>Conclusions:</b> GUANKE exerts anti-RSV effects by enhancing the early type I interferon response and activating the STING-TBK1-IRF3-IFN signaling pathway, thereby inhibiting RSV replication and alleviating pulmonary inflammatory responses. This suggests its potential value as an anti-RSV agent.