Type I IFNs Decrease SARS-CoV-2 Replication in Human Cardiomyocytes and Increase Cytokine Production in Macrophages.

IF 5.7 2区医学 Q1 IMMUNOLOGY

Journal of Clinical Immunology Pub Date : 2025-10-21 DOI:10.1007/s10875-025-01943-6

Verónica Durán, Eirini Nikolouli, Shambhabi Chatterjee, Bibiana Costa, Andreas Pavlou, Annett Ziegler, Jennifer Becker, Kira Baumann, Matthias Bruhn, Kathrin Haake, Anna Rafiei Hashtchin, Ingrid Gensch, Andrea Korte, Yvonne Lisa Behrens, Shen-Ying Zhang, Jean-Laurent Casanova, Christian Bär, Nico Lachmann, Thomas Thum, Ulrich Kalinke

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引用次数: 0

Abstract

The cellular basis of COVID-19 severity in patients with deficiencies in type I IFN immunity remains unclear. In this study, we differentiated cardiomyocytes and macrophages from IFNAR1 competent (IFNAR1^comp) and deficient (IFNAR1^def) induced pluripotent stem cells (iPSCs), and analyzed virus replication and cytokine production after exposure to SARS-CoV-2. Cardiomyocytes expressed the SARS-CoV-2 receptor angiotensin-converting enzyme 2 (ACE2) and showed abundant SARS-CoV-2 replication, which was higher in IFNAR1^def than IFNAR1^comp cells. Treatment with exogenous IFNα mitigated infection in IFNAR1^comp, but not in IFNAR1^def cardiomyocytes. In contrast, macrophages did not express ACE2 and did not support SARS-CoV-2 replication, but produced pro-inflammatory cytokines upon virus exposure, which was impaired in IFNAR1^def macrophages. In conclusion, type I IFNs decrease SARS-CoV-2 replication in human iPSC-derived cardiomyocytes, while they increase cytokine responses of macrophages.

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I型干扰素降低人心肌细胞中SARS-CoV-2的复制并增加巨噬细胞中细胞因子的产生。

I型干扰素免疫缺陷患者中COVID-19严重程度的细胞基础尚不清楚。在这项研究中，我们从IFNAR1激活（IFNAR1comp）和IFNAR1def诱导的多能干细胞（iPSCs）中分化出心肌细胞和巨噬细胞，并分析了暴露于SARS-CoV-2后病毒的复制和细胞因子的产生。心肌细胞表达SARS-CoV-2受体血管紧张素转换酶2 (ACE2)，并表现出丰富的SARS-CoV-2复制，IFNAR1def细胞的复制量高于IFNAR1comp细胞。外源性IFNα治疗可减轻IFNAR1comp的感染，但不能减轻IFNAR1def心肌细胞的感染。相比之下，巨噬细胞不表达ACE2，也不支持SARS-CoV-2复制，但在病毒暴露后产生促炎细胞因子，这在IFNAR1def巨噬细胞中受损。综上所述，I型IFNs可降低人ipsc源性心肌细胞中SARS-CoV-2的复制，同时增加巨噬细胞的细胞因子反应。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Clinical Immunology 医学-免疫学

CiteScore

12.20

自引率

9.90%

发文量

218

审稿时长

2 months

期刊介绍： The Journal of Clinical Immunology publishes impactful papers in the realm of human immunology, delving into the diagnosis, pathogenesis, prognosis, or treatment of human diseases. The journal places particular emphasis on primary immunodeficiencies and related diseases, encompassing inborn errors of immunity in a broad sense, their underlying genotypes, and diverse phenotypes. These phenotypes include infection, malignancy, allergy, auto-inflammation, and autoimmunity. We welcome a broad spectrum of studies in this domain, spanning genetic discovery, clinical description, immunologic assessment, diagnostic approaches, prognosis evaluation, and treatment interventions. Case reports are considered if they are genuinely original and accompanied by a concise review of the relevant medical literature, illustrating how the novel case study advances the field. The instructions to authors provide detailed guidance on the four categories of papers accepted by the journal.