Research ArticleDengue

Increased adaptive immune responses and proper feedback regulation protect against clinical dengue

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Science Translational Medicine  30 Aug 2017:
Vol. 9, Issue 405, eaal5088
DOI: 10.1126/scitranslmed.aal5088

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Distinguishing dengue presentation

Although dengue hemorrhagic fever can be life-threatening, not all dengue virus infections even present with symptoms. To determine what may be driving the differences in clinical and asymptomatic infections, Simon-Lorière et al. examined the serum and immune gene transcripts of Cambodian children infected with dengue virus serotype 1. They saw that relative to those with clinical infections, the small subset of asymptomatic children had increased signs of antigen presentation, T cell activation, and T cell apoptosis; plasmablast differentiation and anti-dengue antibodies seemed relatively lower. These results provide clues for pathways that may drive pathologic responses in severe dengue virus infections.

Abstract

Clinical symptoms of dengue virus (DENV) infection, the most prevalent arthropod-borne viral disease, range from classical mild dengue fever to severe, life-threatening dengue shock syndrome. However, most DENV infections cause few or no symptoms. Asymptomatic DENV-infected patients provide a unique opportunity to decipher the host immune responses leading to virus elimination without negative impact on an individual’s health. We used an integrated approach of transcriptional profiling and immunological analysis to compare a Cambodian population of strictly asymptomatic viremic individuals with clinical dengue patients. Whereas inflammatory pathways and innate immune response pathways were similar between asymptomatic individuals and clinical dengue patients, expression of proteins related to antigen presentation and subsequent T cell and B cell activation pathways was differentially regulated, independent of viral load and previous DENV infection history. Feedback mechanisms controlled the immune response in asymptomatic viremic individuals, as demonstrated by increased activation of T cell apoptosis–related pathways and FcγRIIB (Fcγ receptor IIB) signaling associated with decreased anti-DENV–specific antibody concentrations. Together, our data illustrate that symptom-free DENV infection in children is associated with increased activation of the adaptive immune compartment and proper control mechanisms, leading to elimination of viral infection without excessive immune activation, with implications for novel vaccine development strategies.

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