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