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寄生虫抗原在体外差异调节恢复期 COVID-19 患者 CD4 和 CD8 T 淋巴细胞的激活。

Helminth antigens differentially modulate the activation of CD4 and CD8 T lymphocytes of convalescent COVID-19 patients in vitro.

机构信息

Institute of Medical Microbiology, Immunology and Parasitology (IMMIP), University Hospital Bonn, Sigmund-Freud-Straße 25, 53105, Bonn, Germany.

Unité de Biochimie et de Biologie Moléculaire, Faculté des Sciences et Techniques (FAST), Université d'Abomey-Calavi, Abomey-Calavi, Bénin.

出版信息

BMC Med. 2022 Jun 28;20(1):241. doi: 10.1186/s12916-022-02441-x.

DOI:10.1186/s12916-022-02441-x
PMID:35764965
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9241220/
Abstract

BACKGROUND

The coronavirus disease 2019 (COVID-19) is a respiratory disease caused by SARS-CoV-2, a recently discovered strain of coronavirus. The virus has spread rapidly, causing millions of death worldwide. Contrary to the predictions, prevalence and mortality due to COVID-19 have remained moderate on the African continent. Several factors, including age, genetics, vaccines, and co-infections, might impact the course of the pandemic in Africa. Helminths are highly endemic in Sub-Saharan Africa and are renowned for their ability to evade, skew, and suppress human immune responses through various immune-modulatory mechanisms. Such effects will likely impact SARS-CoV-2 transmission and disease progression.

METHODS

Here, we analyzed in vitro the impact of antigen extracts from three major helminth parasites, including Onchocerca volvulus, Brugia malayi, and Ascaris lumbricoides, on the immune reactivity to SARS-CoV-2 peptides in COVID-19 patients. Activation of CD4 and CD8 T cells was investigated using flow cytometry to monitor the expression of CD137 (4-1BB) and CD69. Cytokine expression, including IL-6, IL-10, IFN-γ, and TNFα, was measured by Luminex in cell culture supernatants.

RESULTS

We observed that helminth antigens significantly reduced the frequency of SARS-CoV-2-reactive CD4 T helper cells. In contrast, the expression of SARS-CoV-2-reactive CD8 T cells was not affected and even significantly increased when PBMCs from COVID-19 patients living in Benin, an endemic helminth country, were used. In addition, stimulation with helminth antigens was associated with increased IL-10 and a reduction of IFNγ and TNFα.

CONCLUSIONS

Our data offer a plausible explanation for the moderate incidence of COVID-19 in Africa and support the hypothesis that helper T cell-mediated immune responses to SARS-CoV-2 are mitigated in the presence of helminth antigens, while virus-specific cytotoxic T cell responses are maintained.

摘要

背景

新型冠状病毒病 2019(COVID-19)是由 SARS-CoV-2 引起的呼吸道疾病,这是一种最近发现的冠状病毒株。该病毒迅速传播,导致全球数百万人死亡。与预测相反,COVID-19 在非洲大陆的流行率和死亡率一直保持中等水平。包括年龄、遗传、疫苗和合并感染在内的多种因素可能会影响非洲大流行的进程。寄生虫在撒哈拉以南非洲高度流行,以其通过各种免疫调节机制逃避、扭曲和抑制人类免疫反应的能力而闻名。这些影响可能会影响 SARS-CoV-2 的传播和疾病进展。

方法

在这里,我们分析了三种主要寄生虫抗原提取物(包括旋毛虫、马来丝虫和蛔虫)对 COVID-19 患者对 SARS-CoV-2 肽的免疫反应的体外影响。通过流式细胞术监测 CD137(4-1BB)和 CD69 的表达来研究 CD4 和 CD8 T 细胞的激活。通过细胞培养上清液中的 Luminex 测量细胞因子表达,包括 IL-6、IL-10、IFN-γ和 TNFα。

结果

我们观察到寄生虫抗原显著降低了 SARS-CoV-2 反应性 CD4 T 辅助细胞的频率。相比之下,当使用来自贝宁(寄生虫流行国家)的 COVID-19 患者的 PBMC 时,SARS-CoV-2 反应性 CD8 T 细胞的表达不受影响,甚至显著增加。此外,用寄生虫抗原刺激与 IL-10 的增加和 IFNγ和 TNFα的减少有关。

结论

我们的数据为 COVID-19 在非洲发病率中等提供了合理的解释,并支持以下假设:在寄生虫抗原存在的情况下,SARS-CoV-2 的辅助性 T 细胞介导的免疫反应被减轻,而病毒特异性细胞毒性 T 细胞反应得以维持。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0d/9241220/a3c7cfc820d2/12916_2022_2441_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0d/9241220/dd5efaa9259f/12916_2022_2441_Fig1_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0d/9241220/1c4930e5772e/12916_2022_2441_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0d/9241220/677d8b4be975/12916_2022_2441_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0d/9241220/a3c7cfc820d2/12916_2022_2441_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0d/9241220/dd5efaa9259f/12916_2022_2441_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0d/9241220/dc03a87b5ced/12916_2022_2441_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0d/9241220/1c4930e5772e/12916_2022_2441_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0d/9241220/677d8b4be975/12916_2022_2441_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2e0d/9241220/a3c7cfc820d2/12916_2022_2441_Fig5_HTML.jpg

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