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Immunophenotyping and transcriptional profiling of human plasmablasts in dengue.

ABSTRACT: Plasmablats are the key cell type involved in Antibody (Ab) production that massively expand in dengue. However, little is known about their molecular profile in dengue . We investigated the transcriptional profiles of plasmablasts from dengue patients. We found that in addition to Ab secretion, they overexpress several molecules related to endothelial interactions, homing to skin or mucosal tisues. Additionally, there are hints for potential involvement in processes such as angiogenesis, leukocyte extravasation and vascular permeability. This is the fisrt detailed transcriptional analysis of plasmablast from dengue patients in India. We use flow cytometry to phenotype these cells and bulk RNA sequencing to analyze their transcriptinal profiles.

ORGANISM(S): Homo sapiens

PROVIDER: GSE171487 | GEO | 2021/09/13

REPOSITORIES: GEO

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Project description: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. We analyzed whole blood samples from 28 dengue patients (DF n=18, DHF=10) hospitalized at the Siriraj Hospital in Bangkok, Thailand during the season of 2009 The specimens were acquired between days 2 and 9 after onset of symptoms (acute illness), and for 19 patients (DF n=13, DHF=6) also at the convalescence at 4 weeks or later after discharge. Additionally, blood was sampled from 9 healthy, non-infected donors to provide controls for transcriptomic and immunological analysis.

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Immunophenotyping and transcriptional profiling of human plasmablasts in dengue.

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