TRIF signaling is essential for the activation of dendritic cells during porcine rotavirus infection.

Rotavirus (RV) infection has become a significant public health risk worldwide, but the specific molecular mechanisms of the mucosal immune response have not been elucidated. Dendritic cells (DCs), professional antigen-presenting cells, have a pivotal role in linking innate and adaptive immunity. In the present study, we found that TIR domain-containing adapter-inducing interferon-β (TRIF) is critical for the activation of DCs to antagonize RV infection. TRIF deficiency limited DCs maturation in the spleen and DCs differentiation in MLNs during porcine rotavirus (PRV) infection. Further studies confirmed that blocking TRIF expression in DCs resulted in an impaired ability to promote T lymphocyte proliferation and differentiation. Mechanistically, TRIF promoted the release of IL-6, IL-10, IL-12, and IFN-γ through the TRAF3-activated NF-κB signaling pathway while helping to activate DCs in MLNs to express MHC-Ⅱ and thus accelerate antigen presentation. Our results establish the concept that a TRIF-dependent positive-feedback loop is critical for sustained DC activation, indicating a novel role for TRIF in PRV-induced mucosal immunity.