Characterization of type I interferon responses in dengue and severe dengue in children in Paraguay

Background: Infection with dengue virus (DENV) produces a wide spectrum of clinical illness ranging from asymptomatic infection to mild febrile illness, and to severe forms of the disease. Type I interferons (IFNs) represent an initial and essential host defense response against viruses. DENV has been reported to trigger a robust type I IFN response; however, IFN-alpha/beta profile in the progression of disease is not well characterized. Objectives and study design: In this context, we conducted a retrospective study assessing the circulating serum levels of type I IFNs and related cytokines at different phases of illness in children during the 2011 outbreak of DENV in Paraguay. Demographic, clinical, laboratory and virological data were analyzed. Results: During defervescence, significantly higher levels of IFN-beta, IL-6 and MIP-1 beta, were detected in severe vs. non-severe dengue patients. Additionally, a significant positive correlation between INF-alpha and viremia was detected in children with severe dengue. A significant positive correlation was also observed between IFN-beta serum levels and hematocrit during the febrile phase, whereas IFN-alpha levels negatively correlated with white blood cells during defervescence in severe dengue patients. Furthermore, previous serologic status of patients to DENV did not influence type I IFN production. Conclusions: The distinct type I IFN profile in children with dengue and severe dengue, as well as its association with viral load, cytokine production and laboratory manifestations indicate differences in innate and adaptive immune responses that should be investigated further in order to unveil the association of immunological and physiological pathways that underlie in DENV infection.