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Humanized mice reveal a macrophage-enriched gene signature defining human lung tissue protection during SARS-CoV-2 infection.
Kenney, Devin J; O'Connell, Aoife K; Turcinovic, Jacquelyn; Montanaro, Paige; Hekman, Ryan M; Tamura, Tomokazu; Berneshawi, Andrew R; Cafiero, Thomas R; Al Abdullatif, Salam; Blum, Benjamin; Goldstein, Stanley I; Heller, Brigitte L; Gertje, Hans P; Bullitt, Esther; Trachtenberg, Alexander J; Chavez, Elizabeth; Nono, Evans Tuekam; Morrison, Catherine; Tseng, Anna E; Sheikh, Amira; Kurnick, Susanna; Grosz, Kyle; Bosmann, Markus; Ericsson, Maria; Huber, Bertrand R; Saeed, Mohsan; Balazs, Alejandro B; Francis, Kevin P; Klose, Alexander; Paragas, Neal; Campbell, Joshua D; Connor, John H; Emili, Andrew; Crossland, Nicholas A; Ploss, Alexander; Douam, Florian.
  • Kenney DJ; Department of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
  • O'Connell AK; Department of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
  • Turcinovic J; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA; Bioinformatics Program, Boston University, Boston, MA, USA.
  • Montanaro P; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA.
  • Hekman RM; Center for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.
  • Tamura T; Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
  • Berneshawi AR; Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
  • Cafiero TR; Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
  • Al Abdullatif S; Single Cell RNA Sequencing Core, Boston University, Boston, MA, USA; Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
  • Blum B; Center for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.
  • Goldstein SI; Center for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.
  • Heller BL; Department of Molecular Biology, Princeton University, Princeton, NJ, USA.
  • Gertje HP; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA.
  • Bullitt E; Department of Physiology and Biophysics, Boston University School of Medicine, Boston, MA, USA.
  • Trachtenberg AJ; Department of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
  • Chavez E; Department of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
  • Nono ET; Department of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
  • Morrison C; Department of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
  • Tseng AE; Department of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
  • Sheikh A; Department of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
  • Kurnick S; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA; Animal Science Center, Boston University, Boston, MA, USA.
  • Grosz K; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA; Animal Science Center, Boston University, Boston, MA, USA.
  • Bosmann M; Department of Medicine, Boston University School of Medicine, Boston, MA, USA; Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, Mainz 55131, Germany.
  • Ericsson M; Electron Microscopy Core Facility, Harvard Medical School, Boston, MA, USA.
  • Huber BR; Department of Neurology, Boston University School of Medicine, Boston, MA, USA.
  • Saeed M; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.
  • Balazs AB; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
  • Francis KP; PerkinElmer, Hopkinton, MA, USA.
  • Klose A; In Vivo Analytics, Inc., New York, NY, USA.
  • Paragas N; In Vivo Analytics, Inc., New York, NY, USA; Department of Radiology Imaging Research Lab, University of Washington, Seattle, WA, USA.
  • Campbell JD; Single Cell RNA Sequencing Core, Boston University, Boston, MA, USA; Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
  • Connor JH; Department of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
  • Emili A; Center for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA; Department of Biology, Boston University School of Medicine, Boston, MA, USA.
  • Crossland NA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA. Electronic address: ncrossla@bu.edu.
  • Ploss A; Department of Molecular Biology, Princeton University, Princeton, NJ, USA. Electronic address: aploss@princeton.edu.
  • Douam F; Department of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA. Electronic address: fdouam@bu.edu.
Cell Rep ; 39(3): 110714, 2022 04 19.
Article in English | MEDLINE | ID: covidwho-1773158
ABSTRACT
The human immunological mechanisms defining the clinical outcome of SARS-CoV-2 infection remain elusive. This knowledge gap is mostly driven by the lack of appropriate experimental platforms recapitulating human immune responses in a controlled human lung environment. Here, we report a mouse model (i.e., HNFL mice) co-engrafted with human fetal lung xenografts (fLX) and a myeloid-enhanced human immune system to identify cellular and molecular correlates of lung protection during SARS-CoV-2 infection. Unlike mice solely engrafted with human fLX, HNFL mice are protected against infection, severe inflammation, and histopathological phenotypes. Lung tissue protection from infection and severe histopathology associates with macrophage infiltration and differentiation and the upregulation of a macrophage-enriched signature composed of 11 specific genes mainly associated with the type I interferon signaling pathway. Our work highlights the HNFL model as a transformative platform to investigate, in controlled experimental settings, human myeloid immune mechanisms governing lung tissue protection during SARS-CoV-2 infection.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Experimental Studies / Prognostic study Limits: Animals / Humans Language: English Journal: Cell Rep Year: 2022 Document Type: Article Affiliation country: J.celrep.2022.110714

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Full text: Available Collection: International databases Database: MEDLINE Main subject: COVID-19 Type of study: Experimental Studies / Prognostic study Limits: Animals / Humans Language: English Journal: Cell Rep Year: 2022 Document Type: Article Affiliation country: J.celrep.2022.110714