Central Role of Dendritic Cells in Shaping the Adaptive Immune Response During Respiratory Syncytial Virus Infection

Abstract

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract disease in young children. Premature infants, immunocompromised individuals and the elderly exhibit the highest risk for the development of severe RSV-induced disease. Murine studies demonstrate that CD8 T cells mediate RSV clearance from the lungs. Murine studies also indicate that the host immune response contributes to RSV-induced morbidity as T-cell depletion prevents the development of disease despite sustained viral replication. Dendritic cells (DCs) play a central role in the induction of the RSV-specific adaptive immune response. Following RSV infection, lung-resident DCs acquire viral antigens, migrate to the lung-draining lymph nodes and initiate the T-cell response. This article focuses on data generated from both in vitro DC infection studies and RSV mouse models that together have advanced our understanding of how RSV infection modulates DC function and the subsequent impact on the adaptive immune response.

Attenuation of Respiratory Syncytial Virus–Induced and RIG-I–Dependent Type I IFN Responses in Human Neonates and Very Young Children

“…Hematopoietic cells are permissive to RSV and may serve as a reservoir for this virus in vivo (34). Dendritic cells play a central role in shaping the immune response to, and outcome of, RSV infection (35,36). In agreement with previous studies (27), we demonstrate that in human hematopoietic cells, type I IFN responses to RSV are primarily mediated by pDCs and are independent of endosomal TLRs.…”

“…Intriguingly, we found pDCs of term neonates to be profoundly impaired in their capacity to produce IFN-a when compared with those of adults, both in response to RSV and in response to a synthetic RIG-I agonist. pDCs are specialized immune cells that infiltrate the lung to produce large amounts of type I IFN in response to viral infection, and they play a pivotal role in the outcome of RSV infection in a mouse model (35,36). In addition, we found the IFN-a production in MNCs in response to RSV Long and a synthetic RIG-I agonist to be lower among children aged 12 mo to , 5 y when compared with the responses among healthy adults.…”

Respiratory syncytial virus infection modifies and accelerates pulmonary disease via DC activation and migration

“…4B and C). Our studies also observed a decrease in RSV-specific mRNA, as might be expected with a local sensitization (data not shown) [41]. Thus, this response suggests that exogenously added DCs alter immune responses to the virus and resulted in increased pathology via Th2 cytokine overproduction in agreement with other studies [42][43][44][45].…”

Respiratory syncytial virus induces indoleamine 2,3‐dioxygenase activity: a potential novel role in the development of allergic disease

“…It is interesting that while an epithelial cell line (HEp-2 cells) released kynurenine in response to IFN-c, this did not occur after RSV infection. As moDCs are critical cells that link innate and adaptive immune responses, including a central role in immune response to RSV [72,73], we focused on moDCs, instead of epithelial cells. Under inflammatory conditions, IDO becomes expressed and activated in dendritic cells [16,17,[69][70][71].…”

“…Under inflammatory conditions, IDO becomes expressed and activated in dendritic cells [16,17,[69][70][71]. As moDCs are critical cells that link innate and adaptive immune responses, including a central role in immune response to RSV [72,73], we focused on moDCs, instead of epithelial cells.…”