Dengue disease is a mosquito-borne viral disease of expanding geographical range and incidence. Infection by one of the four serotypes of dengue virus induces a spectrum of disease manifestations, ranging from asymptomatic to life-threatening Dengue hemorrhagic fever/dengue shock syndrome. Many efforts have been made to elucidate several aspects of dengue virus-induced disease, but the pathogenesis of disease is complex and remains unclear. Understanding the mechanisms involved in the early stages of infection is crucial to determine and develop safe therapeutics to prevent the severe outcomes of disease without interfering with control of infection. In this review, we discuss the dual role of the innate and inflammatory pathways activated during dengue disease in mediating both protection and exacerbation of disease. We show that some mediators involved in each of these responses differ substantially, suggesting that interfering in disease-associated immune pathways may represent a potential therapeutic opportunity for the treatment of severe dengue.
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