Dengue virus infection induces expansion of a CD14+CD16 + monocyte population that stimulates plasmablast differentiation

Marcin Kwissa, Helder I. Nakaya, Nattawat Onlamoon, Jens Wrammert, Francois Villinger, Guey Chuen Perng, Sutee Yoksan, Kovit Pattanapanyasat, Kulkanya Chokephaibulkit, Rafi Ahmed, Bali Pulendran

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96 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)115-127
Number of pages13
JournalCell Host and Microbe
Volume16
Issue number1
DOIs
Publication statusPublished - 2014 Jul 9

All Science Journal Classification (ASJC) codes

  • Parasitology
  • Microbiology
  • Virology

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    Kwissa, M., Nakaya, H. I., Onlamoon, N., Wrammert, J., Villinger, F., Perng, G. C., Yoksan, S., Pattanapanyasat, K., Chokephaibulkit, K., Ahmed, R., & Pulendran, B. (2014). Dengue virus infection induces expansion of a CD14+CD16 + monocyte population that stimulates plasmablast differentiation. Cell Host and Microbe, 16(1), 115-127. https://doi.org/10.1016/j.chom.2014.06.001