IFN signaling and neutrophil degranulation transcriptional signatures are induced during SARS-CoV-2 infection

• Published in: Communications biology Vol. 4; no. 1; p. 290
• Main Authors: Rosa, Bruce A., Ahmed, Mushtaq, Singh, Dhiraj K., Choreño-Parra, José Alberto, Cole, Journey, Jiménez-Álvarez, Luis Armando, Rodríguez-Reyna, Tatiana Sofía, Singh, Bindu, Gonzalez, Olga, Carrion, Ricardo, Schlesinger, Larry S., Martin, John, Zúñiga, Joaquín, Mitreva, Makedonka, Kaushal, Deepak, Khader, Shabaana A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05-03-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 13; 13/51; 38/77; 38/90; 38/91; 631/250/127/1212; 631/250/255/2514; Aged; Animals; Biology; Biomedical and Life Sciences; CD36 Antigens - physiology; Cell Degranulation; Collagen; Collagen - metabolism; Coronaviruses; COVID-19; COVID-19 - etiology; COVID-19 - immunology; Degranulation; Disease Models, Animal; Female; Gene Expression Regulation; Humans; Immunopathogenesis; Infections; Interferon; Interferons - physiology; Leukocytes (neutrophilic); Life Sciences; Lung - metabolism; Lungs; Lymphocytes; Macaca mulatta; Male; Middle Aged; Neutrophils; Neutrophils - physiology; Receptors, Notch - physiology; Risk factors; SARS-CoV-2; Severe acute respiratory syndrome coronavirus 2; Signal transduction; Signal Transduction - physiology; Transcription; Transforming Growth Factor beta - physiology; Tuberculosis; Vascular Endothelial Growth Factor A - blood; Vascular Endothelial Growth Factor A - physiology
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-021-01829-4

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.
Rosa et al. find that genes associated with Interferon (IFN) signaling, neutrophil degranulation and innate immune pathways are induced in the lungs of macaques in response to SARS-CoV-2 infection, whereas genes associated with collagen formation and regulation are reduced. Authors also note an overlap of genes associated with SARS-CoV-2 infection and tuberculosis, altogether providing new insights into the immunopathogenesis of COVID-19 disease.