Submitted by Helder I Nakaya (Emory University, USA) on Oct 28 2013
Platform: microarray – [HT_HG-U133_Plus_PM] Affymetrix HT HG-U133+ PM Array Plate
Pubmed: 24981333
Summary Dengue virus (DENV) infects hundreds of millions of people annually, yet there is only a limited knowledge of the host immune response to dengue. Here, we used a systems biological approach to perform a detailed analysis of the innate immune response to DENV infection in the whole blood samples of acutely infected humans in Bangkok, Thailand. Transcriptomic analysis revealed that genes encoding pro-inflammatory mediators and type I IFN related proteins, were associated with high levels of virus during the first few days of infection. Individuals with low or negative viremia at the late stage of fever were enriched with genes associated with pathways involved in cell cycle, proliferation, cell metabolism and translational control. Meta-analysis showed significant enrichment in genes specific for innate cells (monocytes, macrophages and DCs) in the specimens with high VL and enrichment in genes specific for NK cells, CD4+ and CD8+ T cells as well as B cells in specimens with low VL. Furthermore, flow cytometric analysis revealed an expansion in the numbers of CD14+CD16+ monocytes and depletion of CD14dimCD16++ cells and BDCA-1+ myeloid DC in blood. Consistent with this, in a non-human primate model, infection with DENV boosted the numbers of CD14+CD16+ monocytes in the blood and in secondary lymphoid organs. In vitro, freshly isolated blood monocytes infected with DENV up regulated CD16 and mediated robust differentiation of resting B cells to CD27++CD38++ plasmablasts and IgG and IgM secretion. Taken together, these data provide a detailed picture of the innate response to dengue infection in humans, and highlight an unappreciated role for CD14+CD16+ monocytes in promoting the differentiation of plasmablasts and mediating antibody response to DENV.
ID | Title | Cell Type | Timepoint | Reported Virus | Virus Species | Exclusion Reason |
---|---|---|---|---|---|---|
GSM1253028 | Dengue Fever Patient 3 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253029 | Dengue Fever Patient 4 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253030 | Dengue Fever Patient 6 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253031 | Dengue Fever Patient 7 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253032 | Dengue Hemorrhagic Fever Patient 32 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253033 | Dengue Fever Patient 33 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253034 | Dengue Hemorrhagic Fever Patient 34 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253035 | Dengue Fever Patient 35 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253036 | Dengue Fever Patient 36 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253037 | Dengue Hemorrhagic Fever Patient 81 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253038 | Dengue Fever Patient 37 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253039 | Dengue Hemorrhagic Fever Patient 38 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253040 | Dengue Hemorrhagic Fever Patient 39 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253041 | Dengue Hemorrhagic Fever Patient 40 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253042 | Dengue Fever Patient 41 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253043 | Dengue Fever Patient 42 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253044 | Dengue Fever Patient 43 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253045 | Dengue Fever Patient 44 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253046 | Dengue Hemorrhagic Fever Patient 45 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253047 | Dengue Fever Patient 47 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253048 | Dengue Hemorrhagic Fever Patient 48 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253049 | Dengue Hemorrhagic Fever Patient 49 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253050 | Dengue Fever Patient 54 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253051 | Dengue Fever Patient 55 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253052 | Dengue Hemorrhagic Fever Patient 60 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253053 | Dengue Fever Patient 66 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253054 | Dengue Fever Patient 68 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253055 | Dengue Fever Patient 80 | peripheral blood | acute | DENV | Dengue virus | |
GSM1253056 | Convalescent Patient 3 | peripheral blood | convalescent | DENV | Dengue virus | |
GSM1253057 | Convalescent Patient 4 | peripheral blood | convalescent | DENV | Dengue virus | |
GSM1253058 | Convalescent Patient 6 | peripheral blood | convalescent | DENV | Dengue virus | |
GSM1253059 | Convalescent Patient 33 | peripheral blood | convalescent | DENV | Dengue virus | |
GSM1253060 | Convalescent Patient 34 | peripheral blood | convalescent | DENV | Dengue virus | |
GSM1253061 | Convalescent Patient 35 | peripheral blood | convalescent | DENV | Dengue virus | |
GSM1253062 | Convalescent Patient 36 | peripheral blood | convalescent | DENV | Dengue virus | |
GSM1253063 | Convalescent Patient 37 | peripheral blood | convalescent | DENV | Dengue virus | |
GSM1253064 | Convalescent Patient 38 | peripheral blood | convalescent | DENV | Dengue virus | |
GSM1253065 | Convalescent Patient 39 | peripheral blood | convalescent | DENV | Dengue virus | |
GSM1253066 | Convalescent Patient 41 | peripheral blood | convalescent | DENV | Dengue virus | |
GSM1253067 | Convalescent Patient 44 | peripheral blood | convalescent | DENV | Dengue virus | |
GSM1253068 | Convalescent Patient 45 | peripheral blood | convalescent | DENV | Dengue virus | |
GSM1253069 | Convalescent Patient 47 | peripheral blood | convalescent | DENV | Dengue virus | |
GSM1253070 | Convalescent Patient 48 | peripheral blood | convalescent | DENV | Dengue virus | |
GSM1253071 | Convalescent Patient 49 | peripheral blood | convalescent | DENV | Dengue virus | |
GSM1253072 | Convalescent Patient 54 | peripheral blood | convalescent | DENV | Dengue virus | |
GSM1253073 | Convalescent Patient 55 | peripheral blood | convalescent | DENV | Dengue virus | |
GSM1253074 | Convalescent Patient 80 | peripheral blood | convalescent | DENV | Dengue virus | |
GSM1253075 | Healthy control c3 | peripheral blood | healthy | Uninfected | ||
GSM1253076 | Healthy control c5 | peripheral blood | healthy | Uninfected | ||
GSM1253077 | Healthy control c4 | peripheral blood | healthy | Uninfected | ||
GSM1253078 | Healthy control c6 | peripheral blood | healthy | Uninfected | ||
GSM1253079 | Healthy control c1 | peripheral blood | healthy | Uninfected | ||
GSM1253080 | Healthy control c8 | peripheral blood | healthy | Uninfected | ||
GSM1253081 | Healthy control c7 | peripheral blood | healthy | Uninfected | ||
GSM1253082 | Healthy control c9 | peripheral blood | healthy | Uninfected | ||
GSM1253083 | Healthy control c2 | peripheral blood | healthy | Uninfected |