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急性Q热患者循环单核细胞中持久的转录变化

Long-Lasting Transcriptional Changes in Circulating Monocytes of Acute Q Fever Patients.

作者信息

Raijmakers Ruud Ph, Stenos John, Keijmel Stephan P, Ter Horst Rob, Novakovic Boris, Nguyen Chelsea, Van Der Meer Jos Wm, Netea Mihai G, Bleeker-Rovers Chantal P, Joosten Leo Ab, Graves Stephen R

机构信息

Radboud Expertise Center for Q Fever.

Department of Internal Medicine, Division of Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.

出版信息

Open Forum Infect Dis. 2019 Jul 1;6(7). doi: 10.1093/ofid/ofz296.

Abstract

OBJECTIVE

Although most patients recover from acute Q fever, around 20% develop Q fever fatigue syndrome (QFS), a debilitating fatigue syndrome that lasts at least 6 months. This study investigated transcriptional profiles of circulating monocytes and circulating cytokines as a subsequent mirror of myeloid cell function, 1 and 6 months after an acute Q fever infection.

METHODS

Total RNA of circulating monocytes was collected from 11 acute Q fever patients and 15 healthy controls, matched for age (±5 years) and sex. Samples were collected at a median of 27 days (baseline, interquartile range, 15-35 days) after the infection and again 6 months thereafter. Transcriptome analysis was performed using RNA sequencing. Additionally, concentrations of circulating interleukin (IL)-10, IL-1β, IL-1Ra, and IL-6 were measured in serum.

RESULTS

At baseline, acute Q fever patients clearly show a differential transcriptional program compared with healthy controls. This is still the case at follow-up, albeit to a lesser extent. At baseline, a significant difference in levels of circulating IL-10 (P = .0019), IL-1β (P = .0067), IL-1Ra (P = .0008), and IL-6 (P = .0003) was seen. At follow-up, this difference had decreased for IL-10 (P = .0136) and IL-1Ra (P = .0017) and had become nonsignificant for IL-1β (P = .1139) and IL-6 (P = .2792).

CONCLUSIONS

We show that an acute Q fever infection has a long-term effect on the transcriptional program of circulating monocytes and, therefore, likely their myeloid progenitor cells, as well as concentrations of circulating IL-10, IL-1β, IL-1Ra, and IL-6.

摘要

目的

虽然大多数急性Q热患者可康复,但约20%会发展为Q热疲劳综合征(QFS),这是一种使人衰弱的疲劳综合征,持续至少6个月。本研究调查了急性Q热感染后1个月和6个月时循环单核细胞的转录谱以及循环细胞因子,作为髓样细胞功能的后续反映。

方法

从11例急性Q热患者和15名健康对照者中收集循环单核细胞的总RNA,这些对照者在年龄(±5岁)和性别上相匹配。样本在感染后的中位时间27天(基线,四分位间距,15 - 35天)采集,此后6个月再次采集。使用RNA测序进行转录组分析。此外,测定血清中循环白细胞介素(IL)-10、IL-1β、IL-1Ra和IL-6的浓度。

结果

在基线时,急性Q热患者与健康对照者相比明显表现出不同的转录程序。随访时情况依然如此,尽管程度较轻。在基线时,观察到循环IL-10(P = 0.0019)、IL-1β(P = 0.0067)、IL-1Ra(P = 0.0008)和IL-6(P = 0.0003)水平存在显著差异。随访时,IL-10(P = 0.0136)和IL-1Ra(P = 0.0017)的这种差异减小,而IL-1β(P = 0.1139)和IL-6(P = 0.2792)的差异变得不显著。

结论

我们表明,急性Q热感染对循环单核细胞的转录程序有长期影响,因此可能对其髓样祖细胞以及循环IL-10、IL-1β、IL-1Ra和IL-6的浓度也有长期影响。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/64f7/6667718/bab299a2adb6/ofz296f0001.jpg

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