Respiratory syncytial virus infection of monocyte-derived dendritic cells decreases their capacity to activate CD4 T cells.
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.
de Graaff
Patricia M A
PM
Department of Pediatrics, The Wilhelmina Children's Hospital, University Medical Center, Utrecht, The Netherlands.
de Jong
Esther C
EC
van Capel
Toni M
TM
van Dijk
Mariska E A
ME
Roholl
Paul J M
PJ
Boes
Jolande
J
Luytjes
Willem
W
Kimpen
Jan L L
JL
van Bleek
Grada M
GM
D017951:Antigen Presentation; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000502:physiology* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000502:physiology; D053590:Interleukin 1 Receptor Antagonist Protein; D016753:Interleukin-10 / Q000502:physiology; D008213:Lymphocyte Activation; D009000:Monocytes / Q000166:cytology*; D012136:Respiratory Syncytial Viruses / Q000472:pathogenicity*; D012795:Sialoglycoproteins / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000502:physiology
D016207:Cytokines; C507763:IL1RN protein, human; D016898:Interferon-alpha; D053590:Interleukin 1 Receptor Antagonist Protein; D012795:Sialoglycoproteins; D016753:Interleukin-10