Innate IFNs and pro-inflammatory cytokines in local control of Respiratory Syncytial Virus infection of respiratory epithelial cells.

Abstract

The host innate response contributes to the severity of disease caused by Respiratory Syncytial Virus (RSV). The primary target of RSV is the airway epithelium. The host becomes infected by inhaling droplets containing viral particles, which then infect small foci of cells. Infected cells then express types I and III interferons (IFN) and pro-inflammatory cytokines to alert neighboring epithelial and myeloid cells of danger. Despite their inherent differences, A549 (carcinoma, type II alveolar epithelium) and BEAS-2B (transformed bronchial epithelium) cells are often used interchangeably to study RSV-epithelial interactions. We compared these two cell lines by infecting them with low MOIs of RSV expressing GFP (rgRSV). We measured expression of types I and III IFNs, interferon stimulated genes (ISGs), pro-inflammatory cytokines and signaling intermediaries. We found that BEAS-2B cells contained rgRSV within foci of ~10–15 cells, but all A549 cells were infected by 48h. Both cell lines highly expressed IFN-β, IFN-λ1 and -λ2, but expression was greater in the A549s. Despite lower levels of IFN expression, BEAS-2Bs expressed higher levels of most classic antiviral ISGs (ISG15, MX1, PKR) and critical TLRs, RLRs and IFN receptors. In contrast, A549 cells expressed higher levels of NF-kB associated genes (CCL2, CCL5, CXCL8). Our data suggests that a balance between expression of NF-kB genes and ISGs may determine local control of RSV infection by respiratory epithelial cells.