Immune contacts with T lymphocytes prime dendritic cells against pathogen infection through transfer of exosomal DNA

T cell contacts with antigen-bearing dendritic cells (DCs) result in T cell activation. Whether this interaction has physiological consequences on DC function is largely unexplored. Results associated to this project indicate that antigen-dependent T cell contacts with DCs trigger anti-pathogenic programs in the latter, priming them against pathogen infection. Information is transmitted through extracellular vesicles (EVs) that contain genomic and mitochondrial DNA from the T cell to the DC. T cell transfer of EVs to DCs triggers transcellular antiviral responses that involve the cGAS/STING cytosolic DNA-sensing pathway and expression of IRF3-dependent interferon regulated genes. These events confer resistance to DCs to subsequent viral infections. Together, our results reveal that T cells prime DCs through the transfer of exosomal DNA, supporting a specific role for antigen-dependent contacts in conferring protection to DCs against pathogen infection.