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SARS-CoV-2 Infection of Pluripotent Stem Cell-Derived Human Lung Alveolar Type 2 Cells Elicits a Rapid Epithelial-Intrinsic Inflammatory Response.
Huang, Jessie; Hume, Adam J; Abo, Kristine M; Werder, Rhiannon B; Villacorta-Martin, Carlos; Alysandratos, Konstantinos-Dionysios; Beermann, Mary Lou; Simone-Roach, Chantelle; Lindstrom-Vautrin, Jonathan; Olejnik, Judith; Suder, Ellen L; Bullitt, Esther; Hinds, Anne; Sharma, Arjun; Bosmann, Markus; Wang, Ruobing; Hawkins, Finn; Burks, Eric J; Saeed, Mohsan; Wilson, Andrew A; Mühlberger, Elke; Kotton, Darrell N.
Afiliación
  • Huang J; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
  • Hume AJ; Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118, USA.
  • Abo KM; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
  • Werder RB; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA; QIMR Berghofer Medical Research Institute, Herston, QLD 4006, Australia.
  • Villacorta-Martin C; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA.
  • Alysandratos KD; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
  • Beermann ML; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
  • Simone-Roach C; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; Pulmonary and Respiratory Diseases, Boston Children's Hospital, Boston, MA 02115, USA.
  • Lindstrom-Vautrin J; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA.
  • Olejnik J; Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118, USA.
  • Suder EL; Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118, USA.
  • Bullitt E; Department of Physiology & Biophysics, Boston University, Boston, MA 02118, USA.
  • Hinds A; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
  • Sharma A; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA; Center for Thrombosis and Hemostasis, University Medical Center Mainz, 55131 Mainz, Germany.
  • Bosmann M; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA; Center for Thrombosis and Hemostasis, University Medical Center Mainz, 55131 Mainz, Germany; Research Center for Immunotherapy (FZI), University Medical Center, University of Mainz, Mainz, G
  • Wang R; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; Pulmonary and Respiratory Diseases, Boston Children's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA 02115, USA.
  • Hawkins F; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
  • Burks EJ; Department of Pathology & Laboratory Medicine, Boston University School of Medicine, Boston Medical Center, Boston, MA 02118, USA.
  • Saeed M; Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, USA.
  • Wilson AA; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA. Electronic address: awilson@bu.edu.
  • Mühlberger E; Department of Microbiology, Boston University School of Medicine, Boston, MA 02118, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA 02118, USA. Electronic address: muehlber@bu.edu.
  • Kotton DN; Center for Regenerative Medicine of Boston University and Boston Medical Center, Boston, MA 02118, USA; The Pulmonary Center and Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA; Department of Pathology & Laboratory Medicine, Boston University School of Medicin
Cell Stem Cell ; 27(6): 962-973.e7, 2020 12 03.
Article en En | MEDLINE | ID: mdl-32979316
A hallmark of severe COVID-19 pneumonia is SARS-CoV-2 infection of the facultative progenitors of lung alveoli, the alveolar epithelial type 2 cells (AT2s). However, inability to access these cells from patients, particularly at early stages of disease, limits an understanding of disease inception. Here, we present an in vitro human model that simulates the initial apical infection of alveolar epithelium with SARS-CoV-2 by using induced pluripotent stem cell-derived AT2s that have been adapted to air-liquid interface culture. We find a rapid transcriptomic change in infected cells, characterized by a shift to an inflammatory phenotype with upregulation of NF-κB signaling and loss of the mature alveolar program. Drug testing confirms the efficacy of remdesivir as well as TMPRSS2 protease inhibition, validating a putative mechanism used for viral entry in alveolar cells. Our model system reveals cell-intrinsic responses of a key lung target cell to SARS-CoV-2 infection and should facilitate drug development.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Epiteliales Alveolares / SARS-CoV-2 / Inflamación Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Stem Cell Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Epiteliales Alveolares / SARS-CoV-2 / Inflamación Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Cell Stem Cell Año: 2020 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos