Neonatal dendritic cells alter the immunodominance hierarchy of the CD8 T cell response during influenza infection

Abstract

Abstract Neonates are more susceptible to influenza virus infection than adults, resulting in increased morbidity and mortality as well as delayed clearance of the virus. Multiple differences between the adult and neonatal immune response to influenza help explain this vulnerability. Dendritic cells are of particular interest in this process as their decreased function in neonates results in the poor T cell activation observed during neonatal influenza infections. We sought to understand how differences in neonatal dendritic cells shape CD8 T cell specificity and immunodominance during influenza infection as well as how this may affect memory formation and viral clearance. We found that neonatal C57BL/6 mice display an altered CD8 T cell immunodominance hierarchy, preferentially responding to the influenza protein PA rather than the dominant adult epitope in the NP protein. Additionally, upon secondary infection, mice first infected as pups suffered increased morbidity compared to mice infected previously as adults. Finally, transfer of influenza infected adult dendritic cells to pups resulted in increased T cell activation and enhanced viral clearance. Taken together, these data suggest that neonatal dendritic cells alter CD8 immunodominance, and this may compromise viral clearance and memory formation.