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探讨循环 CXCR5 表达 CD8+T 细胞作为肺炎患者细菌感染生物标志物的作用。

Investigating the role of circulating CXCR5-expressing CD8+ T-cells as a biomarker for bacterial infection in subjects with pneumonia.

机构信息

Clinical Immunology Laboratory, the First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, 215006, China.

Jiangsu Key Laboratory of Clinical Immunology, Soochow University, 708 Renmin Road, Suzhou, 215006, China.

出版信息

Respir Res. 2019 Mar 12;20(1):54. doi: 10.1186/s12931-019-1011-4.

Abstract

BACKGROUND

Recently, lymphoid follicle-confined and circulating CD8+ T-cells expressing the C-X-C chemokine receptor type 5 (CXCR5) were described, which was involved in anti-virus immune response. However, the dynamics and role of circulating CXCR5-expressing CD8+ T-cells during bacterial infection is unknown. So, we asked whether CXCR5+ CD8+ T cells were also generated during bacterial infections in lower respiratory tract.

METHODS

The clinical data of 65 pneumonia patients were analyzed. The patients were divided into groups as tuberculosis, bronchiectasis and community or hospital acquired pneumonia (CAP, HAP). The sputum/bronchial secretion or bronchoalveolar lavage fluid (BALF) samples were taken for microbiological examination. The procalcitonin (PCT) was used to evaluate disease severity of these groups and compared among patients. We characterized the number and phenotype (PD-1 and CD103) of CXCR5 + CD8+ T cells in the peripheral circulation by flow cytometry in all individuals and analyzed their association with the serum PCT level and disease severity.

RESULTS

Patients were mainly infected with Escherichia coli, Acinetobacter baumannii, Klebsiella pneumonia (K.p), Pseudomonas aeruginosa, and Staphylococcus aureus. Of note is the finding that PCT was weakly correlated with severity of respiratory infections. Furthermore, it was revealed an increase of CXCR5-expressing CD8+ T cells in peripheral blood of un-controlled CAP and progressive HAP compared controlled CAP and HAP, respectively (P < 0.05). Strikingly, the circulating CXCR5-expressing CD8+ T-cells in K.p-infected group was higher than that non-K.p-infected group (P < 0.05). Meanwhile, the ratio of CXCR5 + CD8+/CD8 was positively correlated with PCT level (P < 0.05). In clinic, the determination of CXCR5-expressing CD8+ T-cells showed better results compared to PCT and can be useful for the prediction of exacerbation of CAP or HAP. Phenotypically, CXCR5+ CD8 + T cell expressed comparable level of inhibitory molecules PD-1 and lower CD103 compared to their CXCR5- counterparts.

CONCLUSION

The circulating CXCR5-expressing CD8+ T-cell has diagnostic value for current pneumonia severity, and could act as a biomarker for identifying a bacteria-associated exacerbation. These cells may provide novel insight for the pathogenesis of pneumonia.

摘要

背景

最近,人们描述了淋巴滤泡限制和循环 CXCR5 表达的 CD8+T 细胞,其参与了抗病毒免疫反应。然而,在细菌感染期间,循环 CXCR5 表达的 CD8+T 细胞的动态和作用尚不清楚。因此,我们想知道 CXCR5+CD8+T 细胞是否也会在肺部的细菌感染中产生。

方法

分析了 65 例肺炎患者的临床资料。将患者分为肺结核、支气管扩张和社区或医院获得性肺炎(CAP、HAP)组。采集痰/支气管分泌物或支气管肺泡灌洗液(BALF)样本进行微生物学检查。使用降钙素原(PCT)评估这些组的疾病严重程度,并对患者之间进行比较。我们通过流式细胞术对所有个体外周循环中 CXCR5+CD8+T 细胞的数量和表型(PD-1 和 CD103)进行了特征描述,并分析了它们与血清 PCT 水平和疾病严重程度的相关性。

结果

患者主要感染大肠杆菌、鲍曼不动杆菌、肺炎克雷伯菌、铜绿假单胞菌和金黄色葡萄球菌。值得注意的是,发现 PCT 与呼吸道感染的严重程度呈弱相关性。此外,与对照性 CAP 和 HAP 相比,未控制的 CAP 和进行性 HAP 患者外周血中 CXCR5 表达的 CD8+T 细胞增加(P<0.05)。引人注目的是,在 K.p 感染组中循环 CXCR5 表达的 CD8+T 细胞高于非 K.p 感染组(P<0.05)。同时,CXCR5+CD8+/CD8 比值与 PCT 水平呈正相关(P<0.05)。在临床上,与 PCT 相比,CXCR5 表达的 CD8+T 细胞的测定结果更好,可用于预测 CAP 或 HAP 的恶化。表型上,与 CXCR5-相比,CXCR5+CD8+T 细胞表达相似水平的抑制性分子 PD-1 和较低水平的 CD103。

结论

循环 CXCR5 表达的 CD8+T 细胞对当前肺炎严重程度具有诊断价值,可作为识别细菌相关恶化的生物标志物。这些细胞可能为肺炎的发病机制提供新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcfd/6417220/e95d089afd96/12931_2019_1011_Fig1_HTML.jpg

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