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Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates

Author

Listed:
  • M. D. Fahlberg

    (Tulane National Primate Research Center)

  • R. V. Blair

    (Tulane National Primate Research Center
    Department of Pathology and Laboratory Animal Medicine, Tulane University School of Medicine)

  • L. A. Doyle-Meyers

    (Tulane National Primate Research Center
    Department of Medicine, Tulane University School of Medicine)

  • C. C. Midkiff

    (Tulane National Primate Research Center)

  • G. Zenere

    (Tulane National Primate Research Center)

  • K. E. Russell-Lodrigue

    (Tulane National Primate Research Center
    Department of Medicine, Tulane University School of Medicine)

  • C. J. Monjure

    (Tulane National Primate Research Center)

  • E. H. Haupt

    (Tulane National Primate Research Center)

  • T. P. Penney

    (Tulane National Primate Research Center)

  • G. Lehmicke

    (Tulane National Primate Research Center)

  • B. M. Threeton

    (Tulane National Primate Research Center)

  • N. Golden

    (Tulane National Primate Research Center)

  • P. K. Datta

    (Tulane National Primate Research Center
    Department of Pathology and Laboratory Animal Medicine, Tulane University School of Medicine)

  • C. J. Roy

    (Tulane National Primate Research Center
    Department of Microbiology and Immunology, Tulane University School of Medicine)

  • R. P. Bohm

    (Tulane National Primate Research Center
    Department of Medicine, Tulane University School of Medicine)

  • N. J. Maness

    (Tulane National Primate Research Center
    Department of Microbiology and Immunology, Tulane University School of Medicine)

  • T. Fischer

    (Tulane National Primate Research Center
    Department of Microbiology and Immunology, Tulane University School of Medicine)

  • J. Rappaport

    (Tulane National Primate Research Center
    Department of Microbiology and Immunology, Tulane University School of Medicine)

  • M. Vaccari

    (Tulane National Primate Research Center
    Department of Microbiology and Immunology, Tulane University School of Medicine)

Abstract

Understanding SARS-CoV-2 associated immune pathology is crucial to develop pan-effective vaccines and treatments. Here we investigate the immune events from the acute state up to four weeks post SARS-CoV-2 infection, in non-human primates (NHP) with heterogeneous pulmonary pathology. We show a robust migration of CD16 expressing monocytes to the lungs occurring during the acute phase, and we describe two subsets of interstitial macrophages (HLA-DR+CD206−): a transitional CD11c+CD16+ cell population directly associated with IL-6 levels in plasma, and a long-lasting CD11b+CD16+ cell population. Trafficking of monocytes is mediated by TARC (CCL17) and associates with viral load measured in bronchial brushes. We also describe associations between disease outcomes and high levels of cell infiltration in lungs including CD11b+CD16hi macrophages and CD11b+ neutrophils. Accumulation of macrophages is long-lasting and detectable even in animals with mild or no signs of disease. Interestingly, animals with anti-inflammatory responses including high IL-10:IL-6 and kynurenine to tryptophan ratios show less severe illness. Our results unravel cellular mechanisms of COVID-19 and suggest that NHP may be appropriate models to test immune therapies.

Suggested Citation

  • M. D. Fahlberg & R. V. Blair & L. A. Doyle-Meyers & C. C. Midkiff & G. Zenere & K. E. Russell-Lodrigue & C. J. Monjure & E. H. Haupt & T. P. Penney & G. Lehmicke & B. M. Threeton & N. Golden & P. K. D, 2020. "Cellular events of acute, resolving or progressive COVID-19 in SARS-CoV-2 infected non-human primates," Nature Communications, Nature, vol. 11(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-19967-4
    DOI: 10.1038/s41467-020-19967-4
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    Cited by:

    1. Clovis S. Palmer & Chrysostomos Perdios & Mohamed Abdel-Mohsen & Joseph Mudd & Prasun K. Datta & Nicholas J. Maness & Gabrielle Lehmicke & Nadia Golden & Linh Hellmers & Carol Coyne & Kristyn Moore Gr, 2024. "Non-human primate model of long-COVID identifies immune associates of hyperglycemia," Nature Communications, Nature, vol. 15(1), pages 1-18, December.
    2. 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.

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