Submitted by Mehul Shamal Suthar (Emory University, USA) on Aug 26 2019
Platform: ngs – Illumina HiSeq 2500 (Homo sapiens)
Pubmed: None listed
Summary West Nile virus (WNV) is a neurotropic flavivirus and the leading cause of mosquito-borne encephalitis in the United States. Recent studies in humans have found that dysfunctional T cell responses strongly correlate with development of severe WNV neuroinvasive disease. However, the contributions of human dendritic cells (DCs) in priming WNV-specific T cell immunity remains poorly understood. Here, we demonstrate that human monocyte derived DCs (moDCs) support productive viral replication following infection with a pathogenic strain of WNV. Antiviral effector gene transcription was strongly induced during the log-phase viral growth, while secretion of type I interferons (IFN) occurred with delayed kinetics. Activation of RIG-I like receptor (RLR) or type I IFN signaling prior to log-phase viral growth significantly diminished viral replication, suggesting that early activation of antiviral programs can block WNV infection. In contrast to the induction of antiviral responses, WNV infection did not promote transcription or secretion of pro-inflammatory (IL-6, GM-CSF, CCL3, CCL5, CXCL9) or T cell modulatory cytokines (IL-4, IL-12, IL-15). There was also minimal induction of molecules associated with antigen presentation and T cell priming, including the co-stimulatory molecules CD80, CD86, and CD40. Functionally, WNV-infected moDCs dampened allogenic CD4 and CD8 T cell activation and proliferation. Combined, we propose a model where WNV subverts human DC activation to compromise priming of WNV-specific T cell immunity.
ID | Title | Cell Type | Timepoint | Reported Virus | Virus Species | Exclusion Reason |
---|---|---|---|---|---|---|
GSM4047032 | D9_Mock_12H | monocyte-derived dendritic cell | 12 hrs | mock | Uninfected | |
GSM4047033 | D9_Mock_24H | monocyte-derived dendritic cell | 24 hrs | mock | Uninfected | |
GSM4047034 | D9_WNV_12H | monocyte-derived dendritic cell | 12 hrs | WNV | West Nile virus | |
GSM4047035 | D9_WNV_24H | monocyte-derived dendritic cell | 24 hrs | WNV | West Nile virus | |
GSM4047036 | D9_RIG-I_12H | monocyte-derived dendritic cell | 12 hrs | none | Uninfected | Extra interventions RIG-I agonist |
GSM4047037 | D9_MDA5_12H | monocyte-derived dendritic cell | 12 hrs | none | Uninfected | Extra interventions MDA5 agonist |
GSM4047038 | D9_IFNb_12H | monocyte-derived dendritic cell | 12 hrs | none | Uninfected | Extra interventions IFNb agonist |
GSM4047039 | D125_Mock_12H | monocyte-derived dendritic cell | 12 hrs | mock | Uninfected | |
GSM4047040 | D125_Mock_24H | monocyte-derived dendritic cell | 24 hrs | mock | Uninfected | |
GSM4047041 | D125_WNV_12H | monocyte-derived dendritic cell | 12 hrs | WNV | West Nile virus | |
GSM4047042 | D125_WNV_24H | monocyte-derived dendritic cell | 24 hrs | WNV | West Nile virus | |
GSM4047043 | D125_RIG-I_12H | monocyte-derived dendritic cell | 12 hrs | none | Uninfected | Extra interventions RIG-I agonist |
GSM4047044 | D125_MDA5_12H | monocyte-derived dendritic cell | 12 hrs | none | Uninfected | Extra interventions MDA5 agonist |
GSM4047045 | D125_IFNb_12H | monocyte-derived dendritic cell | 12 hrs | none | Uninfected | Extra interventions IFNb agonist |
GSM4047046 | D253_Mock_12H | monocyte-derived dendritic cell | 12 hrs | mock | Uninfected | |
GSM4047047 | D253_Mock_24H | monocyte-derived dendritic cell | 24 hrs | mock | Uninfected | |
GSM4047048 | D253_WNV_12H | monocyte-derived dendritic cell | 12 hrs | WNV | West Nile virus | |
GSM4047049 | D253_WNV_24H | monocyte-derived dendritic cell | 24 hrs | WNV | West Nile virus | |
GSM4047050 | D253_RIG-I_12H | monocyte-derived dendritic cell | 12 hrs | none | Uninfected | Extra interventions RIG-I agonist |
GSM4047051 | D253_MDA5_12H | monocyte-derived dendritic cell | 12 hrs | none | Uninfected | Extra interventions MDA5 agonist |
GSM4047052 | D253_IFNb_12H | monocyte-derived dendritic cell | 12 hrs | none | Uninfected | Extra interventions IFNb agonist |
GSM4047053 | D434_Mock_12H | monocyte-derived dendritic cell | 12 hrs | mock | Uninfected | |
GSM4047054 | D434_Mock_24H | monocyte-derived dendritic cell | 24 hrs | mock | Uninfected | |
GSM4047055 | D434_WNV_12H | monocyte-derived dendritic cell | 12 hrs | WNV | West Nile virus | |
GSM4047056 | D434_WNV_24H | monocyte-derived dendritic cell | 24 hrs | WNV | West Nile virus | |
GSM4047057 | D434_RIG-I_12H | monocyte-derived dendritic cell | 12 hrs | none | Uninfected | Extra interventions RIG-I agonist |
GSM4047058 | D434_MDA5_12H | monocyte-derived dendritic cell | 12 hrs | none | Uninfected | Extra interventions MDA5 agonist |
GSM4047059 | D434_IFNb_12H | monocyte-derived dendritic cell | 12 hrs | none | Uninfected | Extra interventions IFNb agonist |
GSM4047060 | D447_Mock_12H | monocyte-derived dendritic cell | 12 hrs | mock | Uninfected | |
GSM4047061 | D447_Mock_24H | monocyte-derived dendritic cell | 24 hrs | mock | Uninfected | |
GSM4047062 | D447_WNV_12H | monocyte-derived dendritic cell | 12 hrs | WNV | West Nile virus | |
GSM4047063 | D447_WNV_24H | monocyte-derived dendritic cell | 24 hrs | WNV | West Nile virus | |
GSM4047064 | D447_RIG-I_12H | monocyte-derived dendritic cell | 12 hrs | none | Uninfected | Extra interventions RIG-I agonist |
GSM4047065 | D447_MDA5_12H | monocyte-derived dendritic cell | 12 hrs | none | Uninfected | Extra interventions MDA5 agonist |
GSM4047066 | D447_IFNb_12H | monocyte-derived dendritic cell | 12 hrs | none | Uninfected | Extra interventions IFNb agonist |