title: Dengue virus infection induces expansion of a CD14(+)CD16(+) monocyte population that stimulates plasmablast differentiation.
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.
authors: Emory Vaccine Center, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA.
authors: Marcin
authors: M
authors: Kwissa
authors: 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.
authors: Helder I
authors: HI
authors: Nakaya
authors: Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors: Nattawat
authors: N
authors: Onlamoon
authors: 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.
authors: Jens
authors: J
authors: Wrammert
authors: 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.
authors: Francois
authors: F
authors: Villinger
authors: 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.
authors: Guey Chuen
authors: GC
authors: Perng
authors: Insitute of Molecular Biosciences, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors: Sutee
authors: S
authors: Yoksan
authors: Office for Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors: Kovit
authors: K
authors: Pattanapanyasat
authors: Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
authors: Kulkanya
authors: K
authors: Chokephaibulkit
authors: 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.
authors: Rafi
authors: R
authors: Ahmed
authors: 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.
authors: Bali
authors: B
authors: Pulendran
mesh_terms: D000818:Animals; D001769:Blood / Q000276:immunology; D049109:Cell Proliferation; D003715:Dengue / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D006801:Humans; D018950:Lipopolysaccharide Receptors / Q000032:analysis*; D008198:Lymph Nodes / Q000276:immunology; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D009000:Monocytes / Q000737:chemistry / Q000276:immunology*; D010950:Plasma Cells / Q000502:physiology*; D017452:Receptors, IgG / Q000032:analysis*; D017422:Sequence Analysis, DNA
chemical_list: D018950:Lipopolysaccharide Receptors; D017452:Receptors, IgG