Activated peripheral TFH cells and MAIT cells together with increased plasma TNF-α levels mark the pathogenesis of acute dengue virus infection

Abstract

Abstract Dengue virus (DENV) infection has become an increasingly common public health concern in tropical and subtropical regions. Dengue infection appears to cause immune activation in a wide array of immune cells. Here, we estimated Th1 and Th2 cytokines and correlated their levels with primary and secondary dengue. We also investigated the signatures of immune activation of circulating Tfh cells and mucosal-associated invariant T (MAIT) cells in adults with confirmed acute clinical dengue virus infection. We found that IL-2, TNF-α, IL-4, and IL-10 levels were significantly elevated in patients with secondary DENV infection, whereas the level of IL-13 remained unaltered during both primary and secondary infections. No statistically significant difference was noticed with IL-12p70, IL-5, IFN-γ, and GM-CSF between the healthy controls and the primary and secondary dengue. Increase of 1 unit of TNF-α was associated with a decrease of 160 units of blood platelets. We found a higher frequency of activated Tfh cells and pTfh cells in clinical DENV infection. We also found similar activated and expanding phenotypes of MAIT cells. Our study suggests that TNF-α could play a key role in the pathogenesis of dengue along with activated pTfh cells and circulating MAIT cells in acute DENV infection.