Respiratory Syncytial Virus Infection of Monocyte-Derived Dendritic Cells Decreases Their Capacity to Activate CD4 T Cells

Abstract

Respiratory syncytial virus (RSV) is a major cause of severe lower respiratory tract infections in children, the elderly, and immune-compromised individuals. CD4 and CD8 T cells play a crucial role in the elimination of RSV from the infected lung, but T cell memory is not sufficient to completely prevent reinfections. The nature of the adaptive immune response depends on innate immune reactions initiated after interaction of invading pathogens with host APCs. For respiratory pathogens myeloid dendritic cell (DC) precursors that are located underneath the epithelial cell layer lining the airways may play a crucial role in primary activation of T cells and regulating their functional potential. In this study, we investigated the role of human monocyte-derived DC in RSV infection. We showed that monocyte-derived DC can be productively infected, which results in maturation of the DC judged by the up-regulation of CD80, CD83, CD86, and HLA class II molecules. However, RSV infection of DC caused impaired CD4 T cell activation characterized by a lower T cell proliferation and ablation of cytokine production in activated T cells. The suppressive effect was caused by an as yet unidentified soluble factor produced by RSV-infected DC.

Interleukin-15 is associated with disease severity in viral bronchiolitis

“…Finally, absence of PBMC IL-15 upregulation in severe bronchiolitis may reflect a viral pathogenic effect. RSV, for example, has been shown to infect human monocyte-derived DCs in vitro, and impair their ability to subsequently activate and proliferate T-cells [30]. A similar phenomenon might explain the findings in this study.…”

Serum Antibodies Critically Affect Virus-Specific CD4+/CD8+ T Cell Balance during Respiratory Syncytial Virus Infections

“…This finding illustrates the well-documented inhibitory effect of RSV infection on T cell proliferation (28,36,(43)(44)(45)(46). Using expanded virus-specific CD8 + T cell populations, we found similar IFN-g responses induced by HLA class I molecules on both virus-infected APCs and peptideloaded APCs.…”

“…The flow-throughs were enriched CD4 + T cells, CD8 + T cells, or APCs (all populations were .90% pure). In some experiments, monocyte-derived DCs were used as APCs and were produced as described previously (28). In short, monocytes were isolated using CD14 beads (Miltenyi Biotec).…”

Viral–bacterial interactions in the respiratory tract

“…RSV has been reported to render moDCs less efficient in inducing CD4 + T-cell proliferation and cytokine secretion by inducing the release of a soluble mediator that is yet to be identified (de Graaff et al, 2005). Although co-infections were not studied here, the secretion of a soluble mediator affecting T-cell responses could have implications for heterologous infections as well.…”