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

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. Horton, Sydney Hamilton, Hadj Aoued, Justin L. Harper, Christopher T. Edwards, Kevin Nguyen, Kathryn L. Pellegrini, Gregory K. Tharp, Anne Piantadosi, Rebecca D. Levit, Rama R. Amara, Simon M. Barratt-Boyes, Susan P. Ribeiro, Rafick P. Sekaly, Thomas H. Vanderford, Raymond F. Schinazi, Mirko Paiardini () and Steven E. Bosinger ()
Additional contact information
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
Simon M. Barratt-Boyes: 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
Steven E. Bosinger: Emory University

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-37425-9

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