Peripheral Follicular T Helper Cells and Mucosal-Associated Invariant T Cells Represent Activated Phenotypes During the Febrile Phase of Acute Dengue Virus Infection.

Peripheral follicular helper T (pTfh) cells represent specialized CD4+ T cells that help B cells to secrete antibodies. Dengue infection appears to cause immune activation in a wide array of immune cells. Herein, we investigated the signatures of immune activation of circulating Tfh cells and mucosal-associated invariant T (MAIT) cells in adult subjects with confirmed acute clinical dengue virus (DENV) infection by multiparametric flow cytometry. The acute DENV infection induced a significant expansion of highly activated pTfh cells and circulating MAIT cells during acute febrile infection. We found a higher frequency of activated PD-1+ Tfh cells and CD38+ pTfh cells in clinical DENV infection. We also found similar activated and expanding phenotypes of MAIT cells in the patients tested. The total counts of activated pTfh cells and circulating MAIT cells were higher in dengue patients relative to healthy controls. We concluded that pTfh cells and circulating MAIT cells represent activated phenotypes in acute DENV infection.

Increase of Plasma TNF-α Is Associated with Decreased Levels of Blood Platelets in Clinical Dengue Infection.

Dengue virus (DENV) infection has become an increasingly common concern in tropical and subtropical regions. It has protean manifestations ranging from febrile phase to severe life-threatening illness. In this study, we estimated Th1 and Th2 cytokines and correlated the levels with dengue severity along with certain hematological and biochemical parameters. We also studied the seroprevalence of dengue between October and December 2017 at the Government Theni Medical College, India. Individuals with dengue fever (DF) were positive for either IgM or IgG, or both. The biochemical and hematological parameters along with plasma tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), granulocyte monocyte-colony stimulating factor (GM-CSF), interleukin (IL)-13, IL-12p70, IL-10, IL-5, IL-4, and IL-2 cytokines were estimated. The prevalence of DF was 42.9% during the study period. IL-2, TNF-α, IL-4, and IL-10 levels were significantly elevated (p < 0.005) 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 DENV-infected groups. Increase of 1 unit of TNF-α was associated with a decrease of 160 units of blood platelets. Together, the study suggests that TNF-α could play a key role in the pathogenesis of dengue, and despite the decrease in platelet levels, it remains to be seen whether any other inflammatory cells regulate the levels of TNF-α in DENV infection.