I型干扰素特异表达和炎症nocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice
- PMID:26867177
- PMCID:PMC4752723
- DOI:10.1016/j.chom.2016.01.007
I型干扰素特异表达和炎症nocyte-Macrophage Responses Cause Lethal Pneumonia in SARS-CoV-Infected Mice
Abstract
Highly pathogenic human respiratory coronaviruses cause acute lethal disease characterized by exuberant inflammatory responses and lung damage. However, the factors leading to lung pathology are not well understood. Using mice infected with SARS (severe acute respiratory syndrome)-CoV, we show that robust virus replication accompanied by delayed type I interferon (IFN-I) signaling orchestrates inflammatory responses and lung immunopathology with diminished survival. IFN-I remains detectable until after virus titers peak, but early IFN-I administration ameliorates immunopathology. This delayed IFN-I signaling promotes the accumulation of pathogenic inflammatory monocyte-macrophages (IMMs), resulting in elevated lung cytokine/chemokine levels, vascular leakage, and impaired virus-specific T cell responses. Genetic ablation of the IFN-αβ receptor (IFNAR) or IMM depletion protects mice from lethal infection, without affecting viral load. These results demonstrate that IFN-I and IMM promote lethal SARS-CoV infection and identify IFN-I and IMMs as potential therapeutic targets in patients infected with pathogenic coronavirus and perhaps other respiratory viruses.
Copyright © 2016 Elsevier Inc. All rights reserved.
Figures
Comment in
-
SARS-CoV and IFN: Too Little, Too Late.Cell Host Microbe. 2016 Feb 10;19(2):139-41. doi: 10.1016/j.chom.2016.01.012. Cell Host Microbe. 2016. PMID:26867172 Free PMC article.
Similar articles
-
Early upregulation of acute respiratory distress syndrome-associated cytokines promotes lethal disease in an aged-mouse model of severe acute respiratory syndrome coronavirus infection.J Virol. 2009 Jul;83(14):7062-74. doi: 10.1128/JVI.00127-09. Epub 2009 May 6. J Virol. 2009. PMID:19420084 Free PMC article.
-
Induction of interferon-gamma-inducible protein 10 by SARS-CoV infection, interferon alfacon 1 and interferon inducer in human bronchial epithelial Calu-3 cells and BALB/c mice.Antivir Chem Chemother. 2010 Mar 9;20(4):169-77. doi: 10.3851/IMP1477. Antivir Chem Chemother. 2010. PMID:20231782
-
Sex-Based Differences in Susceptibility to Severe Acute Respiratory Syndrome Coronavirus Infection.J Immunol. 2017 May 15;198(10):4046-4053. doi: 10.4049/jimmunol.1601896. Epub 2017 Apr 3. J Immunol. 2017. PMID:28373583 Free PMC article.
-
MyD88 is required for protection from lethal infection with a mouse-adapted SARS-CoV.PLoS Pathog. 2008 Dec;4(12):e1000240. doi: 10.1371/journal.ppat.1000240. Epub 2008 Dec 12. PLoS Pathog. 2008. PMID:19079579 Free PMC article.
-
SARS coronavirus and innate immunity.Virus Res. 2008 Apr;133(1):101-12. doi: 10.1016/j.virusres.2007.03.015. Epub 2007 Apr 23. Virus Res. 2008. PMID:17451827 Free PMC article. Review.
Cited by
-
Comparison of demographic features and laboratory parameters between COVID-19 deceased patients and surviving severe and critically ill cases.World J Clin Cases. 2022 Aug 16;10(23):8161-8169. doi: 10.12998/wjcc.v10.i23.8161. World J Clin Cases. 2022. PMID:36159523 Free PMC article.
-
Cytokine storm-calming property of the isoquinoline alkaloids inCoptis chinensisFranch.Front Pharmacol. 2022 Sep 6;13:973587. doi: 10.3389/fphar.2022.973587. eCollection 2022. Front Pharmacol. 2022. PMID:36147356 Free PMC article. Review.
-
SARS-CoV-2 Non-Structural Proteins and Their Roles in Host Immune Evasion.Viruses. 2022 Sep 8;14(9):1991. doi: 10.3390/v14091991. Viruses. 2022. PMID:36146796 Free PMC article. Review.
-
Indoxyl Sulfate Alters the Humoral Response of the ChAdOx1 COVID-19 Vaccine in Hemodialysis Patients.Vaccines (Basel). 2022 Aug 24;10(9):1378. doi: 10.3390/vaccines10091378. Vaccines (Basel). 2022. PMID:36146454 Free PMC article.
-
Correlation between Type I Interferon Associated Factors and COVID-19 Severity.Int J Mol Sci. 2022 Sep 19;23(18):10968. doi: 10.3390/ijms231810968. Int J Mol Sci. 2022. PMID:36142877 Free PMC article. Review.
References
-
- Blasius A.L Giurisato E。,内堂,施赖伯R。D., Shaw A.S., Colonna M. Bone marrow stromal cell antigen 2 is a specific marker of type I IFN-producing cells in the naive mouse, but a promiscuous cell surface antigen following IFN stimulation. J. Immunol. 2006;177:3260–3265. -PubMed
Publication types
MeSH terms
Substances
Grant support
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Miscellaneous