Lower
respiratory tract infections caused by the paramyxoviruses human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are characterized by short-lasting virus-specific immunity and often long-term airway morbidity, both of which may be the result of alterations in the Ag-presenting function of the lung which follow these
infections. In this study, we investigated whether hMPV and RSV experimental
infections alter the phenotype and function of dendritic cell (DC) subsets that are recruited to the lung. Characterization of lung DC trafficking demonstrated a differential recruitment of plasmacytoid DC (pDC), conventional DC (cDC), and IFN-producing killer DC to the lung and draining lymph nodes after hMPV and
RSV infection. In vitro
infection of lung DC indicated that in pDC, production of IFN-alpha,
TNF-alpha, and CCL5 was induced only by hMPV, whereas CCL3 and CCL4 were induced by both viruses. In cDC, a similar repertoire of
cytokines was induced by hMPV and RSV, except for IFN-beta, which was not induced by RSV. The function of lung pDC was altered following hMPV or
RSV infection in vivo, as we demonstrated a reduced capacity of lung pDC to produce IFN-alpha as well as other
cytokines including
IL-6,
TNF-alpha, CCL2, CCL3, and CCL4 in response to TLR9 stimulation. Moreover, we observed an impaired capacity of cDC from infected mice to present Ag to CD4(+) T cells, an effect that lasted beyond the acute phase of
infection. Our findings suggest that acute paramyxovirus
infections can alter the long-term immune function of pulmonary DC.