Canine adenovirus type 1 induces PANoptosis in canine splenocytes via AIM2 inflammasome activation

Abstract

Canine adenovirus type 1 (CAV-1) is a primary causative agent of infectious hepatitis in canines, posing a significant health threat. Nevertheless, the mechanism by which CAV-1 infection induces a deleterious inflammatory response remains incompletely understood. In this study, two-month-old Beagles were inoculated with a defined dose of CAV-1, and samples were collected from seven organs. Analysis revealed that the expression of AIM2 in primary target organs, the liver and kidney, was not significantly altered. In contrast, AIM2 expression was markedly upregulated in immune organs—specifically the spleen, tonsils, and lymph nodes—where the expression level of the key pyroptotic core protein also increased significantly. Further investigation demonstrated that CAV-1 induced PANoptosis of T cells and B cells in the spleen of infected Beagles. Subsequent in vitro studies using canine splenocytes corroborated these findings and identified that the interaction between CAV-1 double-stranded DNA (dsDNA) and AIM2 initiates PANoptosis. In conclusion, CAV-1 triggers PANoptosis in canine splenocytes by activating the AIM2 inflammasome pathway. Our study reveals the death pathway of canine splenocytes caused by CAV-1 for the first time. These findings provide a foundation for elucidating the mechanism of CAV-1 induced inflammatory response of canine splenocytes.