| Secondary bacterial infections are a common complication following viral infections. In addition, respiratory viral infections have been linked to the development of pulmonary disorders later in life. Dendritic cells (DCs) have been shown to be the primary initiators of the immune response in the lung due to their function as antigen presenting cells (APCs). Therefore we hypothesized that a viral infection of lung DCs results in a decrease in their APC ability creating a state of immunosuppression in the lung, which could lead to the development of further pulmonary disease. To address this question, we infected lung DCs both in vitro and in vivo with a replication deficient adenovirus (Ad) as a model of Ad infection. Ad-infected lung DCs had a decreased ability to stimulate T cell proliferation compared to uninfected controls. This impairment was not due to a decrease in the cell surface expression of MHC class I and II molecules or the costimulatory molecules CD80, CD86, CD40 and OX40L, or a lack of IL-2. Further studies showed that this suppression was not due to a soluble factor, but seemed to be contact-dependent. UV-irradiation of Ad prior to infection abrogated lung DC functional suppression, indicating that viral protein synthesis is required. Examination of T cells demonstrated that Ad-infected DCs were not inducing regulatory T cells. However, T cells reisolated from primary cocultures with Ad-infected DCs were able to proliferate in secondary culture in the presence of IL-2, suggesting that coculture with Ad-infected DCs may induce anergy in the T cells.; In a complementary study, the effects of a vaccinia virus (VV) infection on the function of lung DCs was investigated. In vitro VV infection caused a decrease in lung DC function, with a corresponding downregulation of MHC and costimulatory molecules. In vivo VV infection also resulted in impaired lung DC function, although there was no significant change in phenotype. Analysis of the tryptophan catabolizing enzyme indoleamine 2, 3-dioxygenase (IDO) mRNA revealed an increase in IDO transcripts in lung DCs following in vivo VV infection, suggesting IDO may be involved in the suppression of T cell proliferation. Collectively, these studies suggest that virus infections of lung DCs impair their ability to function as APCs and initiate immune responses. |
