  Dengue is the most prevalent arthropod-borne viral disease. Clinical symptoms
of dengue virus (DENV) infection 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 t v 'health. We used an integrated approach of
transcriptional profiling and immunological analysis comparing a Cambodian
population of strictly asymptomatic viremic individuals with clinical dengue
patients. Whereas inflammatory pathways and innate immune responses were
similar between asymptomatic individuals and clinical dengue patients,
expression of proteins related to antigen presentation and subsequent T and B
cell activation pathways were differentially regulated, independent of viral
load or previous DENV infection. Feedback mechanisms controlled the immune
response in asymptomatic viremic individuals as demonstrated by increased
activation of T cell apoptosis-related pathways and Fc$\gamma$RIIB signaling
associated with decreased anti-DENV specific antibody concentrations. Taken
together, our data illustrate that symptom-free DENV infection in children is
determined by increased activation of the adaptive immune compartment and
proper control mechanisms leading to elimination of viral infection without
excessive immune activation, having implications for novel vaccine development
strategies.
