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

Abstract

Summary of the study: 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 associate with macrophage infiltration and differentiation, and the upregulation of a macrophage-enriched signature composed of eleven 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 setting, human myeloid immune mechanisms governing lung tissue protection during SARS-CoV-2 infection. This Mendeley dataset contains all of the Supplemental Items associated with this study. This includes the following:- Spreadsheet S1. Single-cell RNA sequencing gene-defining clusters and cluster annotation (Excel file).- Spreadsheet S2. Proteomic analysis Matrix; _NRG-L vs. HNFL (Excel file)- Movie S1. Time-lapse (2DPI, 4DPI, 6DPI and 12DPI) 3D in vivo imaging of SARS-CoV-2 infection (mp4 file)- Spreadsheet S3. Phospho-proteomics analysis Matrix; _NRG-L vs. HNFL (Excel file)- Spreadsheet S4. List of differentially expressed genes and IPA scores from bulk RNA sequencing analysis (Excel file).- Spreadsheet S5. List of the mice and fetal donor ID used in this study.THIS DATASET IS ARCHIVED AT DANS/EASY, BUT NOT ACCESSIBLE HERE. TO VIEW A LIST OF FILES AND ACCESS THE FILES IN THIS DATASET CLICK ON THE DOI-LINK ABOV