Humanized mice reveal a macrophage-enriched gene signature defining human lung tissue protection during SARS-CoV-2 infection

• DOI: 10.1016/j.celrep.2022.110714
• Publication Date: 2022-04-04T07:25:13Z
• Authors: Devin J. Kenney; Aoife K. O’Connell; Jacquelyn Turcinovic; Paige Montanaro; Ryan M. Hekman; Tomokazu Tamura; Andrew R. Berneshawi; Thomas R. Cafiero; Salam Al Abdullatif; Benjamin Blum; Stanley I. Goldstein; Brigitte L. Heller; Hans P. Gertje; Esther Bullitt; Alexander J. Trac...; Elizabeth Chavez; Evans Tuekam Nono; Catherine Morrison; Anna E. Tseng; Amira Sheikh; Susanna Kurnick; Kyle Grosz; Markus Bosmann; Maria Ericsson; Bertrand R. Huber; Mohsan Saeed; Alejandro B. Balazs; Kevin P. Francis; Alexander Klose; Neal Paragas; Joshua D. Campbell; John H. Connor; Andrew Emili; Nicholas A. Cross...; Alexander Ploss; Florian Douam
• Keywords: Gene signature; Humanized mouse

The human immunological mechanisms defining the clinical outcome of SARS-CoV-2 infection remain elusive. This knowledge gap is mostly driven by lack appropriate experimental platforms recapitulating immune responses in a controlled lung environment. Here, we report mouse model (i.e., HNFL mice) co-engrafted with fetal xenografts (fLX) and myeloid-enhanced system to identify cellular molecular correlates protection during infection. Unlike mice solely engrafted fLX, are protected against infection, severe inflammation, histopathological phenotypes. Lung tissue from histopathology associates macrophage infiltration differentiation upregulation macrophage-enriched signature composed 11 specific genes mainly associated type I interferon signaling pathway. Our work highlights as transformative platform investigate, settings, myeloid governing