DNGR‐1 is dispensable for CD8+ T‐cell priming during respiratory syncytial virus infection

During respiratory syncytial virus (RSV) infection CD8⁺ T cells both assist in viral clearance and contribute to immunopathology. CD8⁺ T cells recognize viral peptides presented by dendritic cells (DCs), which can directly present viral antigens when infected or, alternatively, “cross‐present” antigens after endocytosis of dead or dying infected cells. Mouse CD8α⁺ and CD103⁺ DCs excel at cross‐presentation, in part because they express the receptor DNGR‐1 that detects dead cells by binding to exposed F‐actin and routes internalized cell debris into the cross‐presentation pathway. As RSV causes death in infected epithelial cells, we tested whether cross‐presentation via DNGR‐1 is necessary for CD8⁺ T‐cell responses to the virus. DNGR‐1‐deficient or wild‐type mice were intranasally inoculated with RSV and the magnitude of RSV‐specific CD8⁺ T‐cell induction was measured. We found that during live RSV infection, cross‐presentation via DNGR‐1 did not have a major role in the generation of RSV–specific CD8⁺ T‐cell responses. However, after intranasal immunization with dead cells infected with RSV, a dependence on DNGR‐1 for RSV‐specific CD8⁺ T‐cell responses was observed, confirming the ascribed role of the receptor. Thus, direct presentation by DCs may be the major pathway initiating CD8⁺ T‐cell responses to RSV, while DNGR‐1‐dependent cross‐presentation has no detectable role.