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Myeloid cell interferon responses correlate with clearance of SARS-CoV-2

pmc: PMC8814034 , PMC8288154
Myeloid cell interferon responses correlate with clearance of SARS-CoV-2
Abstract The emergence of mutant SARS-CoV-2 strains associated with an increased risk of COVID-19-related death necessitates better understanding of the early viral dynamics, host responses and immunopathology. While studies have reported immune profiling using single cell RNA sequencing in terminal human COVID-19 patients, performing longitudinal immune cell dynamics in humans is challenging. Macaques are a suitable model of SARS-CoV-2 infection. We performed longitudinal single-cell RNA sequencing of bronchoalveolar lavage (BAL) cell suspensions from adult rhesus macaques infected with SARS-CoV-2 (n=6) to delineate the early dynamics of immune cells changes. The bronchoalveolar compartment exhibited dynamic changes in transcriptional landscape 3 days post- SARS-CoV-2-infection (3dpi) (peak viremia), relative to 14-17dpi (recovery phase) and pre-infection (baseline). We observed the accumulation of distinct populations of both macrophages and T-lymphocytes expressing strong interferon-driven inflammatory gene signature at 3dpi. Type I IFN response was highly induced in the plasmacytoid dendritic cells. The presence of a distinct HLADR+CD68+CD163+SIGLEC1+ macrophage population exhibiting higher angiotensin converting enzyme 2 (ACE2) expression was also observed. These macrophages were significantly recruited to the lungs of macaques at 3dpi and harbored SARS-CoV-2, while expressing a strong interferon-driven innate anti-viral gene signature. The accumulation of these responses correlated with decline in viremia and recovery. The recruitment of a myeloid cell-mediated Type I IFN response is associated with the rapid clearance of SARS-CoV-2 infection in macaques.
- Americas Society United States
- Tula University Russian Federation
- Szczecin Academy of Arts Poland
- University of Mary United States
- Tulane University United States
Inflammation, Animal, SARS-CoV-2, Science, Macrophages, T-Lymphocytes, Q, Immunity, COVID-19, Antiviral Agents, Bronchoalveolar Lavage, Macaca mulatta, Article, Immunity, Innate, Disease Models, Animal, Disease Models, Interferon Type I, Innate, Animals, Humans, Myeloid Cells, Interferons, Lung
Inflammation, Animal, SARS-CoV-2, Science, Macrophages, T-Lymphocytes, Q, Immunity, COVID-19, Antiviral Agents, Bronchoalveolar Lavage, Macaca mulatta, Article, Immunity, Innate, Disease Models, Animal, Disease Models, Interferon Type I, Innate, Animals, Humans, Myeloid Cells, Interferons, Lung
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