TSLP from RSV-stimulated rat airway epithelial cells activates myeloid dendritic cells

The respiratory syncytial virus (RSV) is a primary cause of lower respiratory tract infections in children, the elderly and in people who are immune suppressed, and is also the cause for the development of asthma primarily in infants. However, the immunological mechanisms by which RSV enhances allergic sensitization and asthma remain unclear. The aim of this study was to examine the influence of RSV-infected airway epithelial cells on the activation and functions of rat myeloid dendritic cells (mDCs). We found that the exposure of primary rat airway epithelial cells (PRAECs) to RSV induced a rapid (6 h), high (12 h) and persistent (18 h) increase in thymic stromal lymphopoietin (TSLP) mRNA compared with untreated PRAECs. TSLP protein expression was also enhanced by RSV infection. Functional maturation of mDCs was induced by RSV-treated PRAECs, as shown by their enhanced levels of OX40L and thymus- and activation-regulated chemokine (TARC) mRNAs, which increased the expressions of major histocompatibility complex II (MHCII) and CD86 costimulatory molecules and promoted enhanced T-cell proliferation in mixed lymphocyte reactions. These activities were inhibited in cocultures with RSV-infected RTECs (rat tracheal epithelial cells, an immortalized cell strain) that had been pretreated with TSLP-targeted small interfering RNA. These results suggest that RSV can induce epithelial cells to produce TSLP, which in turn promotes the maturation of mDCs that might support Th2 cell polarization. Immunology and Cell Biology (2011) 89, 231-238; doi:10.1038/icb.2010.85; published online 6 July 2010