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

• Type of Material: Article
• Authors: Marcin Kwissa, Emory University; Helder Nakaya, Emory University; Nattawat Onlamoon, Mahidol University; Jens Wrammert, Emory University; Francois Villinger, Emory University; Guey Perng, Emory University; Sutee Yoksan, Mahidol University; Kovit Pattanapanyasat, Mahidol University; Kulkanya Chokephaibulkit, Mahidol University; Rafi Ahmed, Emory University; Bali Pulendran, Emory University
• Language: English
• Date: 2014-07-09
• Publisher: Elsevier (Cell Press): 12 month embargo
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2014 Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.chom.2014.06.001
• Title of Journal or Parent Work: Cell Host and Microbe
• ISSN: 1931-3128
• Volume: 16
• Issue: 1
• Start Page: 115
• End Page: 127
• Grant/Funding Information: 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: Microbiology; Virology; GENE TRANSCRIPT ABUNDANCE; SUBCAPSULAR SINUS MACROPHAGES; Parasitology; Science & Technology; HEMORRHAGIC-FEVER; PERIPHERAL-BLOOD; HUMAN DENDRITIC CELLS; IMMUNE-RESPONSES; DISEASE SEVERITY; SYSTEMS BIOLOGY; BLOOD MONONUCLEAR-CELLS; ANTIBODY-DEPENDENT ENHANCEMENT; Life Sciences & Biomedicine
• Research Categories: Biology, Virology; Biology, Microbiology

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.