Format

Send to

Choose Destination
Cell Host Microbe. 2014 Jul 9;16(1):115-27. doi: 10.1016/j.chom.2014.06.001. Epub 2014 Jun 26.

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

Author information

1
Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
2
Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Pathology & Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA.
3
Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
4
Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Microbiology and Immunology, School of Medicine, Emory University, Atlanta, GA 30322, USA.
5
Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Division of Pathology at Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
6
Department of Microbiology and Immunology, Medical College, National Cheng Kung University, Tainan 70101, Taiwan; Center of Infectious Disease and Signaling Research, Medical College, National Cheng Kung University, Tainan 70101, Taiwan.
7
Insitute of Molecular Biosciences, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
8
Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
9
Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA; Department of Pathology & Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA 30322, USA. Electronic address: bpulend@emory.edu.

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.

Comment in

PMID:
24981333
PMCID:
PMC4116428
DOI:
10.1016/j.chom.2014.06.001
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center