Regulatory T cells in acute and chronic human Chikungunya infection

Chikungunya virus (CHIKV) infection generates strong immune responses that are associated with the disease pathophysiology. Regulatory T cells (Treg-cluster of differentiation (CD)-4(+)CD25(high)forkhead box P3 (FOXP3(+))) are essential for the induction and maintenance of peripheral tolerance. Thus, they play key roles in determining the patient prognosis by preventing excessive immune responses via different suppression immune mechanisms. However, the regulatory mechanisms involved in human CHIKV infection are still poorly understood. Here, we characterize for the first time the Treg cell molecule-associated-mechanism during acute and chronic human Chikungunya disease. Here, we assessed the Treg cell population and molecule-associated mechanism in the peripheral blood samples of acute and chronic patients with Chikungunya. Our results indicate that CHIKV infection is associated with reduced frequency of Tregs, along with the impaired expression and production of Treg functional markers, including CD39, CD73, perforin, granzyme, programmed death 1 (PD-1), cytotoxic T lymphocyte antigen (CTLA)-4, and transforming growth factor (TGF)-beta. This observation suggests that Treg cells possess the poor regulatory capacity in both acute and chronic phases of the disease. Taken together, these data provide significant evidence that the imbalanced response of Treg cells plays an essential role in establishing the pathogenesis of Chikungunya. (C) 2021 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

Automated summary

This study characterized the molecular mechanisms associated with regulatory T cells (Tregs) in acute and chronic Chikungunya disease for the first time. The results showed that CHIKV infection is associated with reduced frequency of Tregs and impaired expression and production of Treg functional markers. This suggests that Treg cells have poor regulatory capacity during both acute and chronic phases of the disease. These findings provide significant evidence for the role of imbalanced Treg cell response in the pathogenesis of Chikungunya.