UMMS Affiliation

Division of Infectious Diseases and Immunology, Department of Medicine

Publication Date


Document Type



Amino Acids, Peptides, and Proteins | Hemic and Immune Systems | Immunity | Immunology of Infectious Disease | Immunopathology | Infectious Disease | Virus Diseases | Viruses


BACKGROUND: Hyperendemic circulation of all four types of dengue virus (DENV-1-4) has expanded globally, fueling concern for increased incidence of severe dengue. While the majority of DENV infections are subclinical, epidemiologic studies suggest that type-cross-reactive immunity can influence disease outcome in subsequent infections. The mechanisms controlling these differential clinical outcomes remain poorly defined.

METHODOLOGY/PRINCIPAL FINDINGS: Blood samples were collected from a cohort of school-aged Thai children who subsequently experienced a subclinical DENV infection or developed dengue illness. PBMC collected prior to infection were stimulated in vitro with DENV and the secretion of 30 cytokines was measured using a multiplexed, bead-based array. Significant differences were found in cytokine production based on both the type of DENV used for stimulation and the occurrence of clinical illness. Secretion of IL-15 and MCP-1 was significantly higher by PBMC of subjects who later developed symptomatic DENV infection. In addition, IL-6 was produced by PBMC from all subjects who subsequently developed symptomatic infection, versus 59% of subjects who had subclinical infection. Secretion of IL-12, IL-2R, MIP-1alpha, RANTES, GM-CSF, and TNFalpha was significantly lower by PBMC from subjects with symptomatic infection.

CONCLUSIONS/SIGNIFICANCE: These data demonstrate significant differences in pre-existing immune responses to DENV associated with the clinical outcome of subsequent infection. The finding of higher levels of some cytokines in subjects with symptomatic infection and higher levels of other cytokines in subjects with subclinical infection supports the existence of both protective and pathologic immune profiles. Clinical-immunological correlations identified in the context of natural DENV infection may be useful for evaluating immune responses to dengue vaccines.


Cytokines, Dengue virus, T cells, Dengue fever, Chemokines, Immune response, Vero cells, Secretion

Rights and Permissions

Copyright: This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.

DOI of Published Version



PLoS Negl Trop Dis. 2018 Dec 17;12(12):e0006975. doi: 10.1371/journal.pntd.0006975. eCollection 2018 Dec. Link to article on publisher's site

Journal/Book/Conference Title

PLoS neglected tropical diseases

Related Resources

Link to Article in PubMed

PubMed ID


Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons 1.0 Public Domain Dedication.