Immunology of Infectious Diseases Laboratory of Department of Cellular and Molecular Biology, Federal University of Paraiba, João Pessoa, Paraíba, 58051-900, Brazil.
Post-graduation Program in Biotechnology, Center of Biotechnology of Federal University of Paraíba, João Pessoa, Paraíba, 58051-900, Brazil.
Microbes Infect. 2022 Apr-May;24(3):104927. doi: 10.1016/j.micinf.2021.104927. Epub 2021 Dec 16.
Chikungunya virus (CHIKV) infection generates strong immune responses that are associated with the disease pathophysiology. Regulatory T cells (Treg-cluster of differentiation (CD)-4CD25forkhead 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)-β. 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.
基孔肯雅病毒(CHIKV)感染会引发强烈的免疫反应,这些反应与疾病的病理生理学有关。调节性 T 细胞(Treg-分化簇 4(CD)-4CD25叉头框 P3(FOXP3))对于诱导和维持外周耐受至关重要。因此,它们通过不同的抑制免疫机制,在防止过度免疫反应方面发挥关键作用,从而决定患者的预后。然而,人类 CHIKV 感染涉及的调节机制仍知之甚少。在这里,我们首次描述了急性和慢性人类基孔肯雅病中与 Treg 细胞分子相关的机制。在这里,我们评估了急性和慢性基孔肯雅病患者外周血样本中的 Treg 细胞群体和与分子相关的机制。我们的结果表明,CHIKV 感染与 Treg 细胞频率降低有关,同时 Treg 细胞功能标志物的表达和产生受损,包括 CD39、CD73、穿孔素、颗粒酶、程序性死亡 1(PD-1)、细胞毒性 T 淋巴细胞抗原(CTLA)-4 和转化生长因子(TGF)-β。这一观察表明,Treg 细胞在疾病的急性和慢性阶段都具有较差的调节能力。综上所述,这些数据提供了重要证据,表明 Treg 细胞的失衡反应在基孔肯雅病的发病机制中起着重要作用。