期刊文献

Pre-Existing Allergic Inflammation Alters Both Innate and Adaptive Immune Responses in Mice Co-Infected with Influenza Virus 收藏

预先存在的过敏性炎症改变了与流感病毒共同感染的小鼠的先天和适应性免疫反应

原文求助发布源

作者

Dan Li (https://orcid.org/0009-0004-3035-3461) [1];T. Anienke van der Veen [2];Linsey E. S. de Groot [3];Marina H. de Jager [4];Andy Lan (https://orcid.org/0009-0003-2260-1894) [5];Hoeke A. Baarsma [6];René Lutter (https://orcid.org/0000-0002-6243-9911) [7];Kees van der Graaf [8];Reinoud Gosens (https://orcid.org/0000-0002-5595-152X) [9];Martina Schmidt (https://orcid.org/0000-0003-3075-0630) [10];Barbro N. Melgert (https://orcid.org/0000-0001-7091-907X) [11];

作者单位

[1]Groningen Research Institute of Pharmacy, Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands; [2]Groningen Research Institute of Pharmacy, Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands; [3]Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; [4]Groningen Research Institute of Pharmacy, Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands; [5]Groningen Research Institute of Pharmacy, Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands; [6]Groningen Research Institute of Pharmacy, Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands; [7]Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands; [8]Citeq Biologics BV, 9726 GN Groningen, The Netherlands; [9]Groningen Research Institute of Pharmacy, Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands; [10]Groningen Research Institute of Pharmacy, Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands; [11]Groningen Research Institute of Pharmacy, Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands;

发布日期

2025-4-8

页码

3483

DOI

10.3390/ijms26083483

来源信息

International Journal of Molecular Sciences ISSN：1422-0067, 2025年, 26卷, 8期, 3483页

摘要

Asthma, a chronic airway disease, is marked by allergic inflammation, hyperresponsiveness, and tissue remodeling. Influenza infections in asthma patients can cause severe exacerbations, though the underlying mechanisms remain unclear. This study investigated how pre-existing allergic inflammation affects immune responses to influenza infection in mice exposed to house dust mite (HDM). Mice were repeatedly exposed to HDM, followed by infection with the influenza A virus, and were sacrificed three days post-infection. Plasma was analyzed for HDM-specific immunoglobulins, while lung tissue was used for immune cell flow cytometry and RNA sequencing analysis. HDM exposure induced allergic inflammation, evidenced by more HDM-specific IgE, IgG1, IgG2, eosinophils, neutrophils, Th1, and Th17 cells compared to controls. Upon influenza infection, the effects of HDM and influenza co-infection interacted, showing fewer Th1 cells and regulatory T cells and more Th2 cells compared to mice exposed to the influenza virus alone. Interestingly, RNA-seq analysis revealed less upregulation of Th1-related genes and antiviral pathways in co-exposed mice, suggesting impaired Th1 immunity and antiviral responses. Pre-existing allergic inflammation significantly altered immune responses in mice co-infected with influenza, revealing underdeveloped antiviral responses as early as three days post-infection. These findings may explain the increased susceptibility of patients with asthma to severe viral diseases.

摘要译文

哮喘是一种慢性气道疾病，以过敏性炎症，过度反应性和组织重塑为特征。哮喘患者中的流感感染可能会引起严重的恶化，尽管尚不清楚基本机制。这项研究调查了预先存在的过敏性炎症如何影响暴露于房屋尘螨（HDM）的小鼠中对流感感染的免疫反应。将小鼠反复暴露于HDM，然后感染流感病毒，并在感染后三天处死。分析血浆中HDM特异性免疫球蛋白，而肺组织用于免疫细胞流式细胞仪和RNA测序分析。与对照组相比，HDM暴露诱发了过敏性炎症，这是由更多的HDM特异性IgE，IgG1，IgG2，IgG2，IgG2，嗜酸性粒细胞，嗜中性粒细胞，TH1和TH17细胞与对照组相比所证明的。与单独暴露于流感的小鼠相比，在流感感染感染后，HDM和流感共同感染的作用相互作用，显示出更少的Th1细胞和调节性T细胞以及更多的TH2细胞。有趣的是，RNA-seq分析表明，在相关小鼠中，Th1相关基因和抗病毒途径的上调较少，这表明TH1免疫和抗病毒反应受损。预先存在的过敏性炎症会显着改变与流感共同感染的小鼠的免疫反应，并在感染后三天揭示了较低的抗病毒药反应。这些发现可能解释了哮喘患者对严重病毒疾病的敏感性增加。