TLR2-mediated mucosal immune priming boosts anti-rhabdoviral immunity in early vertebrates

Most pathogens utilize mucosal surfaces to enter and propagate within the host. As one of the main pathogens of fatal and highly contagious diseases, rhabdoviruses are distributed widely in nature affecting both human and animals. Therefore, local mucosal immune responses, most effectively induced by mucosal vaccines, act as frontline immunity to block the pathogens at its initial replication sites. However, the underlying regulatory mechanisms of mucosal immunity triggered by mucosal vaccine remains unclear. Herein, a rhabdoviruses glycoprotein-based mucosal vaccine (G131c) was used to elucidate the regulatory mechanism of local mucosal immunity in zebrafish, a typical immunological model. Firstly, we verified the strong immunoprotection of G131c mucosal vaccine. Furthermore, the delivery kinetics of G131c was evaluated in vivo, indicating the effective uptake of vaccines by mucosal tissues through immersion vaccination. Importantly, we demonstrate immersion with G131c vaccine could activate antigen presenting cells (APCs) at the local mucosal sites, and then arose robust local mucosal and systemic immune responses. More critically, we found that G131c mediated these immune effects by interacting with Toll-like receptor 2 (TLR2) and activating downstream MAPK and NF-κB signaling pathways. Thus, our findings provide previously unappreciated evidence that rhabdovirus glycoprotein could interact with TLR2 and then activate the APCs in local mucosal sites. This study provides a comprehensive perspective on the mechanism of TLR2-mediated mucosal immunity in the early vertebrates.