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Author Notes:

Corresponding author: Bali Pulendran, Emory Vaccine Center, 954 Gatewood Rd., Atlanta, GA 30329, bpulend@emory.edu, tel: 404-712-8945, fax: 404-727-8199

We acknowledge the expertise help of the clinical and supporting staff at the Siriraj Hospital, Bangkok, Thailand.

We warmly acknowledge the exceptional assistance of Stephanie Ehnert, Elizabeth Strobert and all Yerkes NPRC personnel, for their excellent care of the animals and sample collections.

We are very grateful to Jean-Francois Paré from Yerkes NPRC for the outstanding expertise in EM specimen preparation and imaging.

We appreciate a great help of Mohan Maddur Satyanarayana from EVC with MDDC preparation, and Hui-Mien Hsiao from Emory University for the RT-PCR and NS-1 ELISA.

We also thank Kiran Gill and Barbara Cervasi from the EVC Flow Cytometry Core for technical support.

Authors declare no financial conflict of interest that might be construed to influence the results or interpretation of the manuscript.

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Research Funding:

This work was supported by grants from the NIH (R37 DK057665, R37 AI048638, U19 AI090023, U19 AI057266, U54 AI057157, N01 AI50019 and N01 AI50025) and from the Bill & Melinda Gates Foundation to) to Bali Pulendran and PS10D11132 to Yerkes.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Microbiology
  • Parasitology
  • Virology
  • ANTIBODY-DEPENDENT ENHANCEMENT
  • SUBCAPSULAR SINUS MACROPHAGES
  • GENE TRANSCRIPT ABUNDANCE
  • BLOOD MONONUCLEAR-CELLS
  • HUMAN DENDRITIC CELLS
  • HEMORRHAGIC-FEVER
  • PERIPHERAL-BLOOD
  • IMMUNE-RESPONSES
  • DISEASE SEVERITY
  • SYSTEMS BIOLOGY

Dengue Virus Infection Induces Expansion of a CD14(+)CD16(+) Monocyte Population that Stimulates Plasmablast Differentiation

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Journal Title:

Cell Host and Microbe

Volume:

Volume 16, Number 1

Publisher:

, Pages 115-127

Type of Work:

Article | Post-print: After Peer Review

Abstract:

Dengue virus (DENV) infection induces the expansion of plasmablasts, which produce antibodies that can neutralize DENV but also enhance disease upon secondary infection with another DENV serotype. To understand how these immune responses are generated, we used a systems biological approach to analyze immune responses to dengue in humans. Transcriptomic analysis of whole blood revealed that genes encoding proinflammatory mediators and type I interferon-related proteins were associated with high DENV levels during initial symptomatic disease. Additionally, CD14 + CD16 + monocytes increased in the blood. Similarly, in a nonhuman primate model, DENV infection boosted CD14 + CD16 + monocyte numbers in the blood and lymph nodes. Upon DENV infection in vitro, monocytes upregulated CD16 and mediated differentiation of resting B cells to plasmablasts as well as immunoglobulin G (IgG) and IgM secretion. These findings provide a detailed picture of innate responses to dengue and highlight a role for CD14 + CD16 + monocytes in promoting plasmablast differentiation and anti-DENV antibody responses.

Copyright information:

© 2014 Elsevier Inc.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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