Abstract
Active immune suppression can mediate the balance between protective cellular immunity and harmful immunopathology. This suppression can occur locally, at an infection site, or in regional draining lymph nodes (dLNs). Immune regulation is of particular importance in sites such as the lung where aberrant immunopathology can result in loss of tissue function and respiratory failure. We have recently identified a novel population of CD11b+CD103+CCR2+ monocyte-like dendritic cells (MCs) which directly suppress CD8+ T-cell proliferation in vitro. Respiratory infection of mice with RNA viruses recruits these MCs either exclusively to the dLN (after vesicular stomatitis virus infection) or both the dLN and site of viral replication (after influenza infection). Here we show that depletion of MCs from the dLN of mice using CCR2-DTR bone marrow chimeras results in enhanced respiratory CD8+ T-cell responses and lung tissue-resident memory cell (TRM) formation which correlated with enhanced antiviral responses upon heterologous VSV challenge. Conversely, depletion of MCs from both the dLN and respiratory tract following influenza infection results in enhanced respiratory CD8+ T-cell responses coupled with fatal immunopathology. Together, these data suggest that suppressive MCs govern key aspects of respiratory CD8+ T-cell immunity, thereby balancing immunity and adverse pathology in the context of viral infection.