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

• Type of Material: Article
• Authors: Amit Upadhyay, Emory University; Elise G Viox, Emory University; Timothy N Hoang, Emory University; Arun K Boddapati, Emory University; Maria Pino, Emory University; Michelle YH 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 Levit, Emory University; Rama Amara, Emory University; Simon M Barratt-Boyes, University of Pittsburgh; Susan P Ribeiro, Emory University; Rafick-Pierre Sekaly, Emory University; Thomas Vanderford, Emory University; Raymond Schinazi, Emory University; Mirko Paiardini, Emory University; Steven Bosinger, Emory University
• Language: English
• Date: 2023-12-01
• Publisher: Springer Nature Limited
• Publication Version: Final Published Version
• Copyright Statement: © 2023, The Author(s)
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-023-37425-9
• Title of Journal or Parent Work: Nature Communications
• Volume: 14
• Issue: 1
• Start Page: 1914
• End Page: 1914
• Keywords: SARS-CoV-2; Receptors, Immunologic; Cytokines; Membrane Glycoproteins; Macrophages; Animals; Humans; Inflammation; Macaca mulatta; COVID-19

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.