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TREM2+ and interstitial-like macrophages orchestrate airway inflammation in SARS-CoV-2 infection in rhesus macaques

Author

Listed:
  • Amit A. Upadhyay

    (Emory University)

  • Elise G. Viox

    (Emory University)

  • Timothy N. Hoang

    (Emory University)

  • Arun K. Boddapati

    (Emory University)

  • Maria Pino

    (Emory University)

  • Michelle Y.-H. Lee

    (Emory University)

  • Jacqueline Corry

    (University of Pittsburgh)

  • Zachary Strongin

    (Emory University)

  • David A. Cowan

    (Emory University)

  • Elizabeth N. Beagle

    (Emory University)

  • Tristan R. Horton

    (Emory University)

  • Sydney Hamilton

    (Emory University)

  • Hadj Aoued

    (Emory University)

  • Justin L. Harper

    (Emory University)

  • Christopher T. Edwards

    (Emory University)

  • Kevin Nguyen

    (Emory University)

  • Kathryn L. Pellegrini

    (Emory University)

  • Gregory K. Tharp

    (Emory University)

  • Anne Piantadosi

    (Emory University)

  • Rebecca D. Levit

    (Emory University)

  • Rama R. Amara

    (Emory University
    Emory University)

  • Simon M. Barratt-Boyes

    (University of Pittsburgh
    University of Pittsburgh)

  • Susan P. Ribeiro

    (Emory University)

  • Rafick P. Sekaly

    (Emory University)

  • Thomas H. Vanderford

    (Emory University)

  • Raymond F. Schinazi

    (Emory University and Children’s Healthcare of Atlanta)

  • Mirko Paiardini

    (Emory University
    Emory University)

  • Steven E. Bosinger

    (Emory University
    Emory University)

Abstract

The immunopathological mechanisms driving the development of severe COVID-19 remain poorly defined. Here, we utilize a rhesus macaque model of acute SARS-CoV-2 infection to delineate perturbations in the innate immune system. SARS-CoV-2 initiates a rapid infiltration of plasmacytoid dendritic cells into the lower airway, commensurate with IFNA production, natural killer cell activation, and a significant increase of blood CD14-CD16+ monocytes. To dissect the contribution of lung myeloid subsets to airway inflammation, we generate a longitudinal scRNA-Seq dataset of airway cells, and map these subsets to corresponding populations in the human lung. SARS-CoV-2 infection elicits a rapid recruitment of two macrophage subsets: CD163+MRC1-, and TREM2+ populations that are the predominant source of inflammatory cytokines. Treatment with baricitinib (Olumiant®), a JAK1/2 inhibitor is effective in eliminating the influx of non-alveolar macrophages, with a reduction of inflammatory cytokines. This study delineates the major lung macrophage subsets driving airway inflammation during SARS-CoV-2 infection.

Suggested Citation

  • Amit A. Upadhyay & Elise G. Viox & Timothy N. Hoang & Arun K. Boddapati & Maria Pino & Michelle Y.-H. Lee & Jacqueline Corry & Zachary Strongin & David A. Cowan & Elizabeth N. Beagle & Tristan R. Hort, 2023. "TREM2+ and interstitial-like macrophages orchestrate airway inflammation in SARS-CoV-2 infection in rhesus macaques," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-37425-9
    DOI: 10.1038/s41467-023-37425-9
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