Regulation of human paramyxovirus pathogenesis by pulmonary dendritic cells (158.4)

Abstract

Abstract Human metapneumovirus (hMPV), is an important paramyxovirus that is associated with clinical syndromes ranging from mild illnesses, such as common cold, to more devastating conditions, such as bronchiolitis and pneumonia. hMPV has worldwide distribution and high incidence in children, elderly and immunocopromised patients. Understanding the immune mechanisms that regulate hMPV pathogenesis is important clinically for the development of new treatment strategies or novel vaccines for hMPV infection. Respiratory tract dendritic cells (DC) play a fundamental role in the immune system by bridging both innate and adaptive immunity. Therefore, we examined the role of plasmacytoid DC (pDC) in hMPV pathogenesis in an experimental mouse model of infection. Depletion of pDC resulted in an increased viral replication in the lungs from 4.3±1.3×104 to 1.7±6.1×105. However, no change in IFN-α/β production was observed. In addition, pDC-depleted mice demonstrated an exacerbated mucus production and pulmonary inflammation (>60%). Interestingly, the balance of lung DC was altered by the depletion of pDC as the recruitment of classical DC (cDC) into the lungs of infected mice was significantly incremented from 9.9±1.2×105 to 1.7±1.6×106. Finally, the production of CCL20, a DC-attracting chemokine, was also increased after depletion of pDC (>60%). In conclusion, these novel findings demonstrate that pDC play a protective role during hMPV infection by modulation of local immune responses.