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

Author

Listed:
  • Dhiraj K. Singh

    (Texas Biomedical Research Institute)

  • Ekaterina Aladyeva

    (Washington University in St. Louis)

  • Shibali Das

    (Washington University in St. Louis)

  • Bindu Singh

    (Texas Biomedical Research Institute)

  • Ekaterina Esaulova

    (Washington University in St. Louis)

  • Amanda Swain

    (Washington University in St. Louis)

  • Mushtaq Ahmed

    (Washington University in St. Louis)

  • Journey Cole

    (Texas Biomedical Research Institute)

  • Chivonne Moodley

    (Texas Biomedical Research Institute
    Tulane University School of Medicine)

  • Smriti Mehra

    (Texas Biomedical Research Institute)

  • Larry S. Schlesinger

    (Texas Biomedical Research Institute)

  • Maxim N. Artyomov

    (Washington University in St. Louis)

  • Shabaana A. Khader

    (Washington University in St. Louis)

  • Deepak Kaushal

    (Texas Biomedical Research Institute)

Abstract

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. Single cell RNAseq (scRNAseq) allows for the study of individual cells, uncovering heterogeneous and variable responses to environment, infection and inflammation. While studies have reported immune profiling using scRNAseq 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. Our longitudinal scRNAseq of bronchoalveolar lavage (BAL) cell suspensions from young rhesus macaques infected with SARS-CoV-2 (n = 6) demonstrates 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) showing accumulation of distinct populations of both macrophages and T-lymphocytes expressing strong interferon-driven inflammatory gene signature at 3dpi. Type I interferon response is induced in the plasmacytoid dendritic cells with appearance of a distinct HLADR+CD68+CD163+SIGLEC1+ macrophage population exhibiting higher angiotensin-converting enzyme 2 (ACE2) expression. These macrophages are significantly enriched in the lungs of macaques at 3dpi and harbor 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.

Suggested Citation

  • Dhiraj K. Singh & Ekaterina Aladyeva & Shibali Das & Bindu Singh & Ekaterina Esaulova & Amanda Swain & Mushtaq Ahmed & Journey Cole & Chivonne Moodley & Smriti Mehra & Larry S. Schlesinger & Maxim N. , 2022. "Myeloid cell interferon responses correlate with clearance of SARS-CoV-2," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28315-7
    DOI: 10.1038/s41467-022-28315-7
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    1. Jeong Seok Lee & June-Young Koh & Kijong Yi & Young-Il Kim & Su-Jin Park & Eun-Ha Kim & Se-Mi Kim & Sung Ho Park & Young Seok Ju & Young Ki Choi & Su-Hyung Park, 2021. "Single-cell transcriptome of bronchoalveolar lavage fluid reveals sequential change of macrophages during SARS-CoV-2 infection in ferrets," Nature Communications, Nature, vol. 12(1), pages 1-13, December.
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