Study of influenza A virus infection in human dendritic cells and epithelial cells.

Abstract

Influenza A virus (IAV) is an important pathogen which primarily targets epithelial cells of the respiratory tract, but dendritic cells (DCs) residing in the epithelium are also susceptible. DCs play a crucial role in initiating specific adaptive immune response against IAV. In order to determine if IAV replication proceeds differently in DCs and epithelial cells, the susceptibility of these two cell types to IAV, using monocyte-derived DCs (MDDCs) and A549 cell line respectively, was studied. As the maturation status of a DC is critical to its functional performance, the susceptibility of differentially stimulated MDDCs to IAV through activation of different toll-like receptors (TLRs) was also explored. MDDCs supported IAV infection at the expense of cell viability. MDDCs also responded to IAV infection by undergoing maturation. When analysed by flow cytometry, A549 cells exposed to the same dose of IAV were not well infected. Visualization of infection through immunofluorescence staining enabled detection of more infected A549 cells. Maturation of MDDCs via TLR3 and TLR4 partially protected the MDDCs from IAV infection, but not MDDCs matured via TLR7/8. The antiviral activity appears to be dependent on type I interferons (IFNs), as observed through upregulation of IFN-susceptible genes (ISG).