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2019 年冠状病毒病患儿与成人之间存在独特的线粒体介导的 T 细胞凋亡反应。

Distinct Mitochondria-Mediated T-Cell Apoptosis Responses in Children and Adults With Coronavirus Disease 2019.

机构信息

Center for Infection and Immunity and Guangdong Provincial Key Laboratory of Biomedical Imaging, the Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, Guangdong Province, China.

The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Qingyuan, Guangdong Province, China.

出版信息

J Infect Dis. 2021 Oct 28;224(8):1333-1344. doi: 10.1093/infdis/jiab400.

Abstract

BACKGROUND

Lymphopenia is a key feature for adult patients with coronavirus disease 2019 (COVID-19), although it is rarely observed in children. The underlying mechanism remains unclear.

METHODS

Immunohistochemical and flow cytometric analyses were used to compare the apoptotic rate of T cells from COVID-19 adults and children and apoptotic responses of adult and child T cells to COVID-19 pooled plasma. Biological properties of caspases and reactive oxygen species were assessed in T cells treated by COVID-19 pooled plasma.

RESULTS

Mitochondria apoptosis of peripheral T cells were identified in COVID-19 adult patient samples but not in the children. Furthermore, increased tumor necrosis factor-α and interleukin-6 in COVID-19 plasma induced mitochondria apoptosis and caused deoxyribonucleic acid damage by elevating reactive oxygen species levels of the adult T cells. However, the child T cells showed tolerance to mitochondrial apoptosis due to mitochondria autophagy. Activation of autophagy could decrease apoptotic sensitivity of the adult T cells to plasma from COVID-19 patients.

CONCLUSIONS

Our results indicated that the mitochondrial apoptosis pathway was activated in T cells of COVID-19 adult patients specifically, which may shed light on the pathophysiological difference between adults and children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 ).

摘要

背景

淋巴细胞减少是新型冠状病毒疾病 2019(COVID-19)成年患者的一个关键特征,尽管在儿童中很少观察到。其潜在机制尚不清楚。

方法

采用免疫组化和流式细胞术分析比较 COVID-19 成年和儿童 T 细胞的凋亡率以及成年和儿童 T 细胞对 COVID-19 混合血浆的凋亡反应。评估 COVID-19 混合血浆处理的 T 细胞中半胱天冬酶和活性氧的生物学特性。

结果

COVID-19 成年患者样本中存在外周 T 细胞线粒体凋亡,但儿童中不存在。此外,COVID-19 血浆中肿瘤坏死因子-α和白细胞介素-6 的增加通过提高活性氧水平诱导线粒体凋亡,并导致脱氧核糖核酸损伤,导致成年 T 细胞发生线粒体凋亡。然而,儿童 T 细胞由于线粒体自噬而对线粒体凋亡具有耐受性。自噬的激活可以降低成年 T 细胞对 COVID-19 患者血浆的凋亡敏感性。

结论

我们的研究结果表明,COVID-19 成年患者的 T 细胞中特异性地激活了线粒体凋亡途径,这可能揭示了严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)感染的成年和儿童之间的病理生理学差异。

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