IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection
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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.
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Old rhesus macaques infected with SARS-CoV-2 had lower ACE2 levels than young macaques, supporting the idea that ACE2 is dysregulated in the elderly across species.
“a study of SARS-CoV-2 infection in old and juvenile rhesus macaques showed lower levels of ACE2 in old versus young macaques after SARS-CoV-2 infection, supporting the hypothesis that ACE2 is dysregulated in the elderly, even across species67.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [67]
In a rhesus macaque model, old macaques had reduced type I interferon and Notch signalling pathways in their lungs compared with juvenile macaques.
“In a rhesus macaque model of SARS-CoV-2 infection, old macaques also had reduced type I IFN and Notch signaling pathways in their lungs when compared to juvenile counterparts67.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [67]
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Myeloid cell interferon responses correlate with clearance of SARS-CoV-2
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Type I Interferon-Mediated Regulation of Antiviral Capabilities of Neutrophils
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SARS-CoV-2 immunity in animal models
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The Notch Pathway: A Link Between COVID-19 Pathophysiology and Its Cardiovascular Complications
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The role of dendritic cells in COVID-19 infection
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- Authors
- Rosa, B. A., Ahmed, M., Singh, D. K., Choreño-Parra, J. A., Cole, J., Jiménez-Álvarez, L. A., Rodríguez-Reyna, T. S., Singh, B., Gonzalez, O., Carrion, R., Schlesinger, L. S., Martin, J., Zúñiga, J., Mitreva, M., Kaushal, D., & Khader, S. A.
- Affiliations
- Washington University in St. Louis (US)
- Texas Biomedical Research Institute (US)
- Instituto Nacional de Enfermedades Respiratorias (MX)
- Corresponding author
- Mitreva, Makedonka
- Kaushal, Deepak
- Khader, Shabaana A.
- ORCID
- Venue
- Communications Biology
- Published
- 2021-03-05
- Volume
- 4
- Issue
- 1
- Pages
- 290-290
- ISSN
- 2399-3642 (ISSN-L)
- PMC
- PMC7935909
- OpenAlex
- W3135408003
- Cited by
- 106
- References
- 87
- Citations by year
- 2026: 3 · 2025: 16 · 2024: 19 · 2023: 18 · 2022: 25 · 2021: 21 · 2020: 4
- FWCI
- 6.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Communications Biology (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Greater South Information System
- Funders
- U.S. Department of Health and Human Services (HHSO100201700020C)
- Washington University in St. Louis
- Regeneron Pharmaceuticals
- Texas Biomedical Research Institute
- Consejo Nacional de Ciencia y Tecnología (FORDECYT/10SE/2020/05/14-06, FORDECYT/10SE/2020/05/14-07, CVU-737347)
- Institute of Nuclear Energy Research
- Secretaría de Estado de Ciencia, Tecnología e Innovación
- National Institutes of Health (P51OD011103, P51 OD111033, COVID-19, U42OD010442, P51OD011133)
- DHHS Office of the Secretary
- Biomedical Advanced Research and Development Authority (HHSO100201700020C)
- National Institute of Allergy and Infectious Diseases (R01AI134236, R01AI123780)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Keywords
- SARS-CoV-2, COVID-19 pandemic, interferon signaling, neutrophil degranulation, lung transcriptome, rhesus macaque model, age-related susceptibility, type I interferon, Notch signaling, innate immunity, collagen synthesis, neutrophil-to-lymphocyte ratio, immunopathogenesis
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