Blocking of CD1d Decreases Trypanosoma cruzi-Induced Activation of CD4-CD8- T Cells and Modulates the Inflammatory Response in Patients With Chagas Heart Disease
Blocking of CD1d Decreases Trypanosoma cruzi-Induced Activation of CD4-CD8- T Cells and Modulates the Inflammatory Response in Patients With Chagas Heart Disease
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DOI：
10.1093/infdis/jiw266
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发表时间：
2016-09-15
影响因子：
6.4
通讯作者：
Dutra, Walderez Ornelas
中科院分区：
文献类型：
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作者：
Araujo Passos, Livia Silva;Amaral Villani, Fernanda Nobre;Dutra, Walderez Ornelas
控制炎症反应以预防人类恰加斯病中的致命心脏病理是期望的且目前未实现的目标。双阴性（DN）T细胞分别是恰加斯心脏病患者和具有不确定临床形式的恰加斯病的患者中炎性和炎性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的病理学靶点的潜力，我们研究了CD 1分子参与克氏锥虫特异性DN T细胞的激活和功能概况。我们观察到寄生虫刺激显著增加了恰加斯病患者CD 14（+）细胞的CD 1a、CD 1b、CD 1c和CD 1d表达。重要的是，在分析的分子中，只有CD 1d表达与DN T细胞的活化有关，以及与查加斯病患者的心室功能较差有关。阻断CD 1d介导的抗原呈递导致DN T细胞活化明显减少，DN T细胞干扰素γ（IFN-γ）表达减少。因此，我们的研究结果表明，通过CD 1d的抗原呈递与查加斯病中DN T细胞的活化相关，并且CD 1d阻断导致查加斯心脏病患者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。
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 gamma (IFN-gamma) 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-gamma by DN T cells from patients with Chagas heart disease, which may be a potential target for preventing progression of inflammation-mediated dilated cardiomyopathy.