Respiratory syncytial virus infection of alveolar macrophages in adult transplant patients.

Pulmonary epithelial cells are thought to be the primary cellular targets for infection by respiratory syncytial virus (RSV) in vivo. To determine whether other pulmonary cells are infected by RSV, bronchoalveolar lavage cells from six adult transplant patients, four of whom had acute RSV infection, were examined by in situ immunohistochemistry to identify infected lung cells. Both alveolar macrophages and epithelial cells were infected with RSV in vivo. At the single-cell level, three-color immunofluorescent studies revealed that both RSV-infected epithelial cells and alveolar macrophages expressed Class II molecules of the major histocompatibility complex, but only the alveolar macrophage coexpressed interleukin-1 beta. Paraformaldehyde-fixed bronchoalveolar lavage cells from RSV-infected but not uninfected patients induced a marked proliferative response by cloned T cells indicating that in vivo infected cells expressed bioactive interleukin-1. Together, these studies indicate that the alveolar macrophage may have a critical role in the lung immune response to RSV.

Restricted replication of respiratory syncytial virus in human alveolar macrophages.

The cellular factors that regulate infection and replication of respiratory syncytial virus (RSV) in human alveolar macrophages were examined. RSV-exposed alveolar macrophages demonstrated a time-dependent expression of viral glycoproteins, maximal by 24 h post-infection resulting in infection of approx. 38% of the cells. Essentially all (33%) of these freshly isolated alveolar macrophages replicated RSV as shown by infectious centre assays. This RSV-permissive subpopulation of alveolar macrophages consisted primarily of major histocompatibility class II-expressing cells as determined by fluorescence-activated cell sorting. Re-infection of alveolar macrophages did not significantly alter the number of cells infected or capable of replicating RSV. However, in vitro differentiation of alveolar macrophages prior to infection resulted in a significant (P < 0.05), time-dependent decrease (approx. sevenfold) in the number of cells that replicated virus. The mechanism by which cellular differentiation restricted RSV replication is unknown. Production of defective interfering particles did not account for this decrease. Alveolar macrophages infected with RSV produce a variety of cytokines potentially contributing to this restricted viral replication. Pretreatment with several of these cytokines did not affect viral infection or replication. However, tumour necrosis factor (TNF alpha) significantly (P < 0.05) decreased viral replication but only by 30 to 60%. Thus RSV replication is reduced by in vitro differentiation of alveolar macrophages and, to a lesser degree, by pretreatment with TNF.