1. RIG-I-like Receptor Triggering by Dengue Virus Drives Dendritic Cell Immune Activation and T
- Author
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Joris K, Sprokholt, Tanja M, Kaptein, John L, van Hamme, Ronald J, Overmars, Sonja I, Gringhuis, and Teunis B H, Geijtenbeek
- Subjects
Interferon-Induced Helicase, IFIH1 ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Interleukin-1beta ,Cell Differentiation ,Dendritic Cells ,Dengue Virus ,Th1 Cells ,Interferon-gamma ,DEAD Box Protein 58 ,Humans ,Receptors, Immunologic ,Chemokine CCL4 ,Chemokine CCL2 ,Chemokine CCL3 - Abstract
Dengue virus (DENV) causes 400 million infections annually and is one of several viruses that can cause viral hemorrhagic fever, which is characterized by uncontrolled immune activation resulting in high fever and internal bleeding. Although the underlying mechanisms are unknown, massive cytokine secretion is thought to be involved. Dendritic cells (DCs) are the main target cells of DENV, and we investigated their role in DENV-induced cytokine production and adaptive immune responses. DENV infection induced DC maturation and secretion of IL-1β, IL-6, and TNF. Inhibition of DENV RNA replication abrogated these responses. Notably, silencing of RNA sensors RIG-I or MDA5 abrogated DC maturation, as well as cytokine responses by DENV-infected DCs. DC maturation was induced by type I IFN responses because inhibition of IFN-α/β receptor signaling abrogated DENV-induced DC maturation. Moreover, DENV infection of DCs resulted in CCL2, CCL3, and CCL4 expression, which was abrogated after RIG-I and MDA5 silencing. DCs play an essential role in T
- Published
- 2016