IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection
Open Access
- 5 March 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Communications Biology
- Vol. 4 (1), 1-14
- https://doi.org/10.1038/s42003-021-01829-4
Abstract
SARS-CoV-2 virus has infected more than 92 million people worldwide resulting in the Coronavirus disease 2019 (COVID-19). Using a rhesus macaque model of SARS-CoV-2 infection, we have characterized the transcriptional signatures induced in the lungs of juvenile and old macaques following infection. Genes associated with Interferon (IFN) signaling, neutrophil degranulation and innate immune pathways are significantly induced in macaque infected lungs, while pathways associated with collagen formation are downregulated, as also seen in lungs of macaques with tuberculosis. In COVID-19, increasing age is a significant risk factor for poor prognosis and increased mortality. Type I IFN and Notch signaling pathways are significantly upregulated in lungs of juvenile infected macaques when compared with old infected macaques. These results are corroborated with increased peripheral neutrophil counts and neutrophil lymphocyte ratio in older individuals with COVID-19 disease. Together, our transcriptomic studies have delineated disease pathways that improve our understanding of the immunopathogenesis of COVID-19.This publication has 87 references indexed in Scilit:
- STAR: ultrafast universal RNA-seq alignerBioinformatics, 2012
- The Sequence Read ArchiveNucleic Acids Research, 2010
- Differential expression analysis for sequence count dataGenome Biology, 2010
- CD36, a Scavenger Receptor Involved in Immunity, Metabolism, Angiogenesis, and BehaviorScience Signaling, 2009
- Interferon-Mediated Immunopathological Events Are Associated with Atypical Innate and Adaptive Immune Responses in Patients with Severe Acute Respiratory SyndromeJournal of Virology, 2007
- Crosslinking of CD66b on Peripheral Blood Neutrophils Mediates the Release of Interleukin-8 from Intracellular StorageHuman Immunology, 2006
- Observation of an unexpected third receptor molecule in the crystal structure of human interferon-γ receptor complexStructure, 2000
- The Jak Kinases Differentially Associate with the α and β (Accessory Factor) Chains of the Interferon γ Receptor to Form a Functional Receptor Unit Capable of Activating STAT Transcription FactorsOnline Journal of Public Health Informatics, 1995
- Molecular cloning and expression of the human interferon-γ receptorCell, 1988
- The Lymphocyte Function Associated LFA-1, CD2, and LFA-3 Molecules: Cell Adhesion Receptors of the Immune SystemAnnual Review of Immunology, 1987