@article{203281,
  keywords = {COVID-19, CP: Immunology, CP: Microbiology, antiviral responses, human immune responses to SARS-CoV-2, humanized mice, macrophage responses to SARS-CoV-2, mouse models of SARS-CoV-2, pulmonary immune responses},
  author = {Devin Kenney and Aoife O{\textquoteright}Connell and Jacquelyn Turcinovic and Paige Montanaro and Ryan Hekman and Tomokazu Tamura and Andrew Berneshawi and Thomas Cafiero and Salam Abdullatif and Benjamin Blum and Stanley Goldstein and Brigitte Heller and Hans Gertje and Esther Bullitt and Alexander Trachtenberg and Elizabeth Chavez and Evans Nono and Catherine Morrison and Anna Tseng and Amira Sheikh and Susanna Kurnick and Kyle Grosz and Markus Bosmann and Maria Ericsson and Bertrand Huber and Mohsan Saeed and Alejandro Balazs and Kevin Francis and Alexander Klose and Neal Paragas and Joshua Campbell and John Connor and Andrew Emili and Nicholas Crossland and Alexander Ploss and Florian Douam},
  title = {Humanized mice reveal a macrophage-enriched gene signature defining human lung tissue protection during SARS-CoV-2 infection.},
  abstract = {<p>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.</p>
},
  year = {2022},
  journal = {Cell reports},
  volume = {39},
  pages = {110714},
  month = {04/2022},
  issn = {2211-1247},
  doi = {10.1016/j.celrep.2022.110714},
  language = {eng},
}