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Lung Spatial Profiling Reveals a T Cell Signature in COPD Patients with Fatal SARS-CoV-2 Infection.
Yang, Chen Xi; Tomchaney, Michael; Landecho, Manuel F; Zamacona, Borja R; Marin Oto, Marta; Zulueta, Javier; Malo, Joshua; Knoper, Steve; Contoli, Marco; Papi, Alberto; Vasilescu, Dragos M; Sauler, Maor; Straub, Christof; Tan, Cheryl; Martinez, Fernando D; Bhattacharya, Deepta; Rosas, Ivan O; Kheradmand, Farrah; Hackett, Tillie-Louise; Polverino, Francesca.
Afiliación
  • Yang CX; Centre for Heart and Lung Innovation, St. Paul's Hospital, Vancouver, BC V6T 1Z4, Canada.
  • Tomchaney M; Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
  • Landecho MF; Asthma and Airway Disease Research Center, College of Medicine, University of Arizona College of Medicine, Tucson, AZ 85719, USA.
  • Zamacona BR; Department of Internal Medicine, Clinica Universidad de Navarra, 31008 Pamplona, Spain.
  • Marin Oto M; Department of Internal Medicine, Clinica Universidad de Navarra, 31008 Pamplona, Spain.
  • Zulueta J; Department of Internal Medicine, Clinica Universidad de Navarra, 31008 Pamplona, Spain.
  • Malo J; Mount-Sinai Hospital, New York, NY 10029, USA.
  • Knoper S; Department of Surgery, University of Arizona, Tucson, AZ 85719, USA.
  • Contoli M; Department of Surgery, University of Arizona, Tucson, AZ 85719, USA.
  • Papi A; Pulmonary Division, University of Ferrara, 44121 Ferrara, Italy.
  • Vasilescu DM; Pulmonary Division, University of Ferrara, 44121 Ferrara, Italy.
  • Sauler M; Centre for Heart and Lung Innovation, St. Paul's Hospital, Vancouver, BC V6T 1Z4, Canada.
  • Straub C; Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
  • Tan C; Department of Medicine, Yale University, New Haven, CT 06520, USA.
  • Martinez FD; Nanostring Technologies, Seattle, WA 98109, USA.
  • Bhattacharya D; Nanostring Technologies, Seattle, WA 98109, USA.
  • Rosas IO; Asthma and Airway Disease Research Center, College of Medicine, University of Arizona College of Medicine, Tucson, AZ 85719, USA.
  • Kheradmand F; Department of Immunobiology, University of Arizona, Tucson, AZ 85719, USA.
  • Hackett TL; Department of Medicine and Center for Translational Research, Baylor College of Medicine, Houston, TX 77030, USA.
  • Polverino F; Department of Medicine and Center for Translational Research, Baylor College of Medicine, Houston, TX 77030, USA.
Cells ; 11(12)2022 06 07.
Article en En | MEDLINE | ID: mdl-35740993
People with pre-existing lung diseases such as chronic obstructive pulmonary disease (COPD) are more likely to get very sick from SARS-CoV-2 disease 2019 (COVID-19). Still, an interrogation of the immune response to COVID-19 infection, spatially throughout the lung structure, is lacking in patients with COPD. For this study, we characterized the immune microenvironment of the lung parenchyma, airways, and vessels of never- and ever-smokers with or without COPD, all of whom died of COVID-19, using spatial transcriptomic and proteomic profiling. The parenchyma, airways, and vessels of COPD patients, compared to control lungs had (1) significant enrichment for lung-resident CD45RO+ memory CD4+ T cells; (2) downregulation of genes associated with T cell antigen priming and memory T cell differentiation; and (3) higher expression of proteins associated with SARS-CoV-2 entry and primary receptor ubiquitously across the ROIs and in particular the lung parenchyma, despite similar SARS-CoV-2 structural gene expression levels. In conclusion, the lung parenchyma, airways, and vessels of COPD patients have increased T-lymphocytes with a blunted memory CD4 T cell response and a more invasive SARS-CoV-2 infection pattern and may underlie the higher death toll observed with COVID-19.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad Pulmonar Obstructiva Crónica / COVID-19 Límite: Humans Idioma: En Revista: Cells Año: 2022 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Suiza
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad Pulmonar Obstructiva Crónica / COVID-19 Límite: Humans Idioma: En Revista: Cells Año: 2022 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Suiza