Impairment of lung dendritic cell antigen presenting capacity by human paramyxovirus infections

Abstract

Respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) are major etiologic agents of severe respiratory tract infections. We have recently shown that both CD4+ and CD8+ T cells are virtually absent in lung of fatal cases of RSV‐positive lower respiratory tract infections, suggesting that this pathogen can severely inhibit T cell responses. Pulmonary dendritic cells (DC) are critical in regulating T cell‐mediated immune response in the respiratory tract. Therefore, we examined the effect of RSV and hMPV infections on the capacity of lung dendritic cells to stimulate T cells. RSV and hMPV induced a peak of CD11C+/MHC‐II+ DC recruitment (>3×106) to the lung by day 8 and 10, respectively. DC remained elevated by day 18 (1×106), when no virus is detected, compared to DC recruited in control mice (1×105). The capacity of lung DC to present antigen to T cells was impaired by RSV or hMPV infection as DC from infected mice showed a reduced capacity (> 65%) to present OVA peptide to CD4+ T cells, compared to DC from control mice. The impairment was observed despite the fact that MHC‐II and CD80 were upregulated. Importantly, we observed that expression of the negative T cell regulator PDL‐1 was also upregulated on DC from infected mice. In conclusion, this study demonstrates that RSV and hMPV may evade immune response by suppressing DC‐mediated T cell proliferation.NIH P01 062885, Flight Attendant Medical Research Institute