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

• Published in: Cell host & microbe Vol. 16; no. 1; pp. 115 - 127
• Main Authors: Kwissa, Marcin, Nakaya, Helder I., Onlamoon, Nattawat, Wrammert, Jens, Villinger, Francois, Perng, Guey Chuen, Yoksan, Sutee, Pattanapanyasat, Kovit, Chokephaibulkit, Kulkanya, Ahmed, Rafi, Pulendran, Bali
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 09.07.2014
• Subjects: Animals; Blood - immunology; Cell Proliferation; Dengue - immunology; Dengue Virus - immunology; Disease Models, Animal; Gene Expression Profiling; Humans; Lipopolysaccharide Receptors - analysis; Lymph Nodes - immunology; Macaca mulatta; Molecular Sequence Data; Monocytes - chemistry; Monocytes - immunology; Plasma Cells - physiology; Receptors, IgG - analysis; Sequence Analysis, DNA
• ISSN: 1931-3128; 1934-6069; 1934-6069
• DOI: 10.1016/j.chom.2014.06.001

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. [Display omitted] •Transcriptional response to dengue depends on viral burden and duration of illness•Expansion of CD14+CD16+ monocyte population in acute dengue infection in humans•Enhanced CD14+CD16+ monocyte numbers in lymph nodes of dengue-infected macaques•Dengue-infected CD14+CD16+ monocytes induce differentiation of plasmablasts Dengue infection in humans induces a potent inflammatory response and expansion of antibody-producing plasmablasts in the blood. By performing a systems biological analysis of innate responses to dengue, Kwissa et al. highlight a role for CD14+CD16+ monocytes in promoting the differentiation of plasmablasts and mediating antibody responses to dengue virus.