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TREM2+ and interstitial-like macrophages orchestrate airway inflammation in SARS-CoV-2 infection in rhesus macaques.
Upadhyay, Amit A; Viox, Elise G; Hoang, Timothy N; Boddapati, Arun K; Pino, Maria; Lee, Michelle Y-H; Corry, Jacqueline; Strongin, Zachary; Cowan, David A; Beagle, Elizabeth N; Horton, Tristan R; Hamilton, Sydney; Aoued, Hadj; Harper, Justin L; Edwards, Christopher T; Nguyen, Kevin; Pellegrini, Kathryn L; Tharp, Gregory K; Piantadosi, Anne; Levit, Rebecca D; Amara, Rama R; Barratt-Boyes, Simon M; Ribeiro, Susan P; Sekaly, Rafick P; Vanderford, Thomas H; Schinazi, Raymond F; Paiardini, Mirko; Bosinger, Steven E.
  • Upadhyay AA; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Viox EG; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Hoang TN; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Boddapati AK; Emory NPRC Genomics Core Laboratory, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Pino M; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Lee MY; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Corry J; Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA.
  • Strongin Z; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Cowan DA; Emory NPRC Genomics Core Laboratory, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Beagle EN; Emory NPRC Genomics Core Laboratory, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Horton TR; Emory NPRC Genomics Core Laboratory, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Hamilton S; Emory NPRC Genomics Core Laboratory, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Aoued H; Emory NPRC Genomics Core Laboratory, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Harper JL; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Edwards CT; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Nguyen K; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Pellegrini KL; Emory NPRC Genomics Core Laboratory, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Tharp GK; Emory NPRC Genomics Core Laboratory, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Piantadosi A; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, USA.
  • Levit RD; Department of Medicine, School of Medicine, Emory University, Atlanta, GA, USA.
  • Amara RR; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Barratt-Boyes SM; Department of Microbiology and Immunology, Emory School of Medicine, Emory University, Atlanta, GA, USA.
  • Ribeiro SP; Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA.
  • Sekaly RP; Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA.
  • Vanderford TH; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, USA.
  • Schinazi RF; Department of Pathology and Laboratory Medicine, School of Medicine, Emory University, Atlanta, GA, USA.
  • Paiardini M; Division of Microbiology and Immunology, Emory National Primate Research Center, Emory University, Atlanta, GA, USA.
  • Bosinger SE; Department of Pediatrics, School of Medicine, Emory University and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Nat Commun ; 14(1): 1914, 2023 04 06.
Article in English | MEDLINE | ID: covidwho-2284905
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Prognostic study Limits: Animals / Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2023 Document Type: Article Affiliation country: S41467-023-37425-9

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Prognostic study Limits: Animals / Humans Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2023 Document Type: Article Affiliation country: S41467-023-37425-9