Dengue Virus-Specific Humoral and T Cellular Immune Response in Italian Residents and Travelers Returning from Endemic Areas

Dengue virus (DENV), a member of the family Flaviviridae, is the causative agent of dengue fever, the most prevalent mosquito-borne viral illness in humans, representing a major public health concern in the tropical countries. Although humoral immunity to DENV has been extensively studied and widely used, little is known about the potential diagnostic use of T cell response for DENV diagnosis. The aim of our study was to characterize the T cell immunity in subjects with acute or past DENV infection, using an original and easy to perform ex vivo ELISpot assay, and to evaluate the role of cross-reactivity between the four DENV serotypes and between DENV and Zika virus (ZIKV). As controls, DENV-seronegative healthy subjects were enrolled and a cutoff of positive DENV-specific T cell response was calculated. DENV-specific T cell response for at least one DENV serotype was detected among all DENV-specific neutralization positive subject. Furthermore, our data showed that in acute DENV infection, the DENV-specific effector memory T cell response against the relevant serotype was predominant. However, a high level of cross-reactivity among all DENV serotypes was also documented. DENV-specific T cell response was almost undetectable among DENV-seronegative subjects with ZIKV acute infection, supporting the hypothesis that the assay could be useful in differential diagnosis between ZIKV and DENV infection.