Passos Lívia Silva Araújo, Villani Fernanda Nobre Amaral, Magalhães Luísa Mourão Dias, Gollob Kenneth J, Antonelli Lis Ribeiro do Vale, Nunes Maria Carmo Pereira, Dutra Walderez Ornelas
Department of Morphology Parasitology Graduate Program, Institute of Biological Sciences.
Department of Morphology.
J Infect Dis. 2016 Sep 15;214(6):935-44. doi: 10.1093/infdis/jiw266. Epub 2016 Jul 1.
The control of inflammatory responses to prevent the deadly cardiac pathology in human Chagas disease is a desirable and currently unattained goal. Double-negative (DN) T cells are important sources of inflammatory and antiinflammatory cytokines in patients with Chagas heart disease and those with the indeterminate clinical form of Chagas disease, respectively. Given the importance of DN T cells in immunoregulatory processes and their potential as targets for controlling inflammation-induced pathology, we studied the involvement of CD1 molecules in the activation and functional profile of Trypanosoma cruzi-specific DN T cells. We observed that parasite stimulation significantly increased the expression of CD1a, CD1b, CD1c, and CD1d by CD14(+) cells from patients with Chagas disease. Importantly, among the analyzed molecules, only CD1d expression showed an association with the activation of DN T cells, as well as with worse ventricular function in patients with Chagas disease. Blocking of CD1d-mediated antigen presentation led to a clear reduction of DN T-cell activation and a decrease in the expression of interferon γ (IFN-γ) by DN T cells. Thus, our results showed that antigen presentation via CD1d is associated with activation of DN T cells in Chagas disease and that CD1d blocking leads to downregulation of IFN-γ by DN T cells from patients with Chagas heart disease, which may be a potential target for preventing progression of inflammation-mediated dilated cardiomyopathy.
控制炎症反应以预防人类恰加斯病中的致命性心脏病变是一个理想但目前尚未实现的目标。双阴性（DN）T细胞分别是恰加斯心脏病患者和恰加斯病不确定临床形式患者炎症和抗炎细胞因子的重要来源。鉴于DN T细胞在免疫调节过程中的重要性及其作为控制炎症诱导病变靶点的潜力，我们研究了CD1分子在克氏锥虫特异性DN T细胞激活和功能特征中的作用。我们观察到，寄生虫刺激显著增加了恰加斯病患者CD14(+)细胞中CD1a、CD1b、CD1c和CD1d的表达。重要的是，在所分析的分子中，只有CD1d表达与DN T细胞的激活以及恰加斯病患者较差的心室功能相关。阻断CD1d介导的抗原呈递导致DN T细胞激活明显减少，且DN T细胞中干扰素γ（IFN-γ）表达降低。因此，我们的结果表明，通过CD1d的抗原呈递与恰加斯病中DN T细胞的激活相关，并且阻断CD1d会导致恰加斯心脏病患者的DN T细胞下调IFN-γ，这可能是预防炎症介导的扩张型心肌病进展的潜在靶点。
