Activation, Impaired Tumor Necrosis Factor-α Production, and Deficiency of Circulating Mucosal-Associated Invariant T Cells in Patients with Scrub Typhus
Activation, Impaired Tumor Necrosis Factor-α Production, and Deficiency of Circulating Mucosal-Associated Invariant T Cells in Patients with Scrub Typhus
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DOI：
10.1371/journal.pntd.0004832
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发表时间：
2016-07-01
影响因子：
3.8
通讯作者：
Park, Yong-Wook
中科院分区：
文献类型：
--
作者：
Kang, Seung-Ji;Jin, Hye-Mi;Park, Yong-Wook
背景粘膜相关不变 T (MAIT) 细胞有助于防止某些微生物感染。然而，人们对 MAIT 细胞在恙虫病东方体感染中的作用知之甚少。因此，本研究的目的是检查恙虫病患者中 MAIT 细胞的水平和功能，并评估 MAIT 细胞水平的临床相关性。 方法/主要发现 38 名恙虫病患者和 53 名健康对照受试者参加了该研究。根据疾病严重程度将患者进一步分为亚组。通过流式细胞术测量外周血中MAIT细胞的水平和功能。研究发现，恙虫病患者的循环 MAIT 细胞水平显着降低。 MAIT 细胞缺陷反映了多种临床状况。特别是，MAT 细胞水平反映了疾病的严重程度。恙虫病患者的 MAIT 细胞显示肿瘤坏死因子 (TNF)-α 的产生受损，但在缓解期恢复。此外，MAIT 细胞产生的 TNF-α 受损与 CD69 表达升高有关。结论本研究表明，恙虫病患者的循环 MAIT 细胞在 TNF-α 产生方面被激活、数量不足且功能受损。这些异常可能导致恙虫病感染中的免疫系统失调。
BackgroundMucosal-associated invariant T (MAIT) cells contribute to protection against certain microorganism infections. However, little is known about the role of MAIT cells in Orientia tsutsugamushi infection. Hence, the aims of this study were to examine the level and function of MAIT cells in patients with scrub typhus and to evaluate the clinical relevance of MAIT cell levels.Methodology/Principal FindingsThirty-eight patients with scrub typhus and 53 health control subjects were enrolled in the study. The patients were further divided into subgroups according to disease severity. MAIT cell level and function in the peripheral blood were measured by flow cytometry. Circulating MAIT cell levels were found to be significantly reduced in scrub typhus patients. MAIT cell deficiency reflects a variety of clinical conditions. In particular, MAT cell levels reflect disease severity. MAIT cells in scrub typhus patients displayed impaired tumor necrosis factor (TNF)-alpha production, which was restored during the remission phase. In addition, the impaired production of TNF-alpha by MAIT cells was associated with elevated CD69 expression.ConclusionsThis study shows that circulating MAIT cells are activated, numerically deficient, and functionally impaired in TNF-a production in patients with scrub typhus. These abnormalities possibly contribute to immune system dysregulation in scrub typhus infection.