Distinct SARS-CoV-2 specific NLRP3 and IL-1β responses in T cells of aging patients during acute COVID-19 infection.
Distinct SARS-CoV-2 specific NLRP3 and IL-1β responses in T cells of aging patients during acute COVID-19 infection.
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DOI：
10.3389/fimmu.2023.1231087
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发表时间：
2023
影响因子：
7.3
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中科院分区：
文献类型：
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严重急性呼吸综合征冠状病毒2（SARS-CoV-2）引起2019冠状病毒病（COVID-19），临床表现多样，从无症状或轻度感染和肺炎到与细胞因子风暴相关的严重病例，急性呼吸窘迫综合征（ARDS），甚至死亡。导致这些差异的潜在机制尚不清楚，尽管感染导致的炎症后遗症加剧已被提及。虽然高龄是一个已知的风险因素，但决定老年人SARS-CoV-2感染结果的精确免疫参数尚不清楚。在这里，我们发现与年龄≤ 60岁的个体相比，T细胞反应的衰老相关（年龄≥61岁）内在变化，即使在症状轻微的COVID阳性患者中也是如此。具体而言，当在体外用SARS-CoV-2肽刺激时，来自≥61岁个体的外周血单核细胞（PBMC）CD 4+和CD 8 + T细胞显示出产生IFN-γ和IL-1β的能力降低。尽管他们没有严重的疾病，但老年人在SARS-CoV-2肽刺激后也显示出更高的PD-1+细胞频率和T淋巴细胞中IFN-γ/PD-1比值显著降低。T细胞IL-1β表达受损与T淋巴细胞中NLRP 3水平降低一致。然而，这些分子的表达在≥61岁个体的单核细胞中不受影响。总之，这些数据揭示了61岁以上个体中SARS-CoV-2特异性CD 4+和CD 8 + T细胞内在细胞因子的变化，并可能为老年人中COVID-2介导的免疫反应失调提供新的见解。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19) that presents with varied clinical manifestations ranging from asymptomatic or mild infections and pneumonia to severe cases associated with cytokine storm, acute respiratory distress syndrome (ARDS), and even death. The underlying mechanisms contributing to these differences are unclear, although exacerbated inflammatory sequelae resulting from infection have been implicated. While advanced aging is a known risk factor, the precise immune parameters that determine the outcome of SARS-CoV-2 infection in elderly individuals are not understood. Here, we found aging-associated (age ≥61) intrinsic changes in T cell responses when compared to those from individuals aged ≤ 60, even among COVID-positive patients with mild symptoms. Specifically, when stimulated with SARS-CoV-2 peptides in vitro, peripheral blood mononuclear cell (PBMC) CD4+ and CD8+ T cells from individuals aged ≥61 showed a diminished capacity to produce IFN-γ and IL-1β. Although they did not have severe disease, aged individuals also showed a higher frequency of PD-1+ cells and significantly diminished IFN-γ/PD-1 ratios among T lymphocytes upon SARS-CoV-2 peptide stimulation. Impaired T cell IL-1β expression coincided with reduced NLRP3 levels in T lymphocytes. However, the expression of these molecules was not affected in the monocytes of individuals aged ≥61. Together, these data reveal SARS-CoV-2-specific CD4+ and CD8+ T-cell intrinsic cytokine alterations in the individuals older than 61 and may provide new insights into dysregulated COVID-directed immune responses in the elderly.