ArticleCell reports2022
Humanized mice reveal a macrophage-enriched gene signature defining human lung tissue protection during SARS-CoV-2 infection.
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Article in Cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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24citing papers in PubMed
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Who cites it
24 citing papers in PubMed, 32 citations in OpenAlex.
- Triple IFN pathway deficiency sensitizes mice to human respiratory virus infection independent of human viral receptor expression.Nature communications · 2026Article
- Humanized immune system animal models and their recent applications.Animal models and experimental medicine · 2026Review
- A Lung-Immune Dual-Humanized Mouse Using Cryopreserved Tissue Enables Infection and Immune Profiling of Human Common Cold Coronaviruses.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Immune signatures of SARS-CoV-2 infection resolution in human lung tissues.PLoS pathogens · 2025Article
- IL-4 and TGF-β regulate inflammatory cytokines and cellular infiltration in the lung and systemic IL-6 in mouse-adapted SARS-CoV-2 infection.ImmunoHorizons · 2025Article
- Complete substitution with modified nucleotides in self-amplifying RNA suppresses the interferon response and increases potency.Nature biotechnology · 2025Article
- T Cell Development and Responses in Human Immune System Mice.Annual review of immunology · 2025Review
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- Challenging the notion of endothelial infection by SARS-CoV-2: insights from the current scientific evidence.Frontiers in immunology · 2025Article
- Akaluc bioluminescence offers superior sensitivity to trackiScience · 2024Article
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- The inflammatory microenvironment of the lung at the time of infection governs innate control of SARS-CoV-2 replication.bioRxiv : the preprint server for biology · 2024Article
- Heat Inactivation of Nipah Virus for Downstream Single-Cell RNA Sequencing Does Not Interfere with Sample Quality.Pathogens (Basel, Switzerland) · 2024Article
- Aging is associated with an insufficient early inflammatory response of lung endothelial cells in SARS-CoV-2 infection.Frontiers in immunology · 2024Article
- Article
- SARS-CoV-2 Omicron (B.1.1.529) shows minimal neurotropism in a double-humanized mouse model.Antiviral research · 2023Article
- Positive-strand RNA viruses-a Keystone Symposia report.Annals of the New York Academy of Sciences · 2023Article
- Recent Developments in NSG and NRG Humanized Mouse Models for Their Use in Viral and Immune Research.Viruses · 2023Review
- A virological view of tenascin-C in infection.American journal of physiology. Cell physiology · 2023Review
- A humanized "new-trophil" mouse to study early inflammatory processes.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
Corrections and comments
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Authors and funding
36 authors at 7 institutions in 2 countries.
Devin J KenneyDepartment of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
Aoife K O'ConnellDepartment of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
Jacquelyn TurcinovicNational Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA; Bioinformatics Program, Boston University, Boston, MA, USA.
Paige MontanaroNational Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA.
Ryan M HekmanCenter for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.
Tomokazu TamuraDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.
Andrew R BerneshawiDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.
Thomas R CafieroDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.
Salam Al AbdullatifSingle Cell RNA Sequencing Core, Boston University, Boston, MA, USA; Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
Benjamin BlumCenter for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.
Stanley I GoldsteinCenter for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.
Brigitte L HellerDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA.
Hans P GertjeNational Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA.
Esther BullittDepartment of Physiology and Biophysics, Boston University School of Medicine, Boston, MA, USA.
Alexander J TrachtenbergDepartment of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
Elizabeth ChavezDepartment of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
Evans Tuekam NonoDepartment of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
Catherine MorrisonDepartment of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
Anna E TsengDepartment of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
Amira SheikhDepartment of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
Susanna KurnickNational Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA; Animal Science Center, Boston University, Boston, MA, USA.
Kyle GroszNational Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA; Animal Science Center, Boston University, Boston, MA, USA.
Markus BosmannDepartment of Medicine, Boston University School of Medicine, Boston, MA, USA; Center for Thrombosis and Hemostasis, University Medical Center of the Johannes Gutenberg-University, Mainz 55131, Germany.
Maria EricssonElectron Microscopy Core Facility, Harvard Medical School, Boston, MA, USA.
Bertrand R HuberDepartment of Neurology, Boston University School of Medicine, Boston, MA, USA.
Mohsan SaeedNational Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA.
Alejandro B BalazsRagon Institute of MGH, MIT and Harvard, Cambridge, MA, USA.
Kevin P FrancisPerkinElmer, Hopkinton, MA, USA.
Alexander KloseIn Vivo Analytics, Inc., New York, NY, USA.
Neal ParagasIn Vivo Analytics, Inc., New York, NY, USA; Department of Radiology Imaging Research Lab, University of Washington, Seattle, WA, USA.
Joshua D CampbellSingle Cell RNA Sequencing Core, Boston University, Boston, MA, USA; Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
John H ConnorDepartment of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA.
Andrew EmiliCenter for Network Systems Biology, Boston University, Boston, MA, USA; Department of Biochemistry, Boston University School of Medicine, Boston, MA, USA; Department of Biology, Boston University School of Medicine, Boston, MA, USA.
Nicholas A CrosslandNational Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA; Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA, USA. Electronic address: ncrossla@bu.edu.
Alexander PlossDepartment of Molecular Biology, Princeton University, Princeton, NJ, USA. Electronic address: aploss@princeton.edu.
Florian DouamDepartment of Microbiology, Boston University School of Medicine, Boston, MA, USA; National Emerging Infectious Diseases Laboratories, Boston University, Boston, MA, USA. Electronic address: fdouam@bu.edu.
Boston University · USPrinceton University · USHarvard University · USInVivo Analytics (United States) · USPerkinElmer (United States) · USRagon Institute of MGH, MIT and Harvard · USUniversity of Washington · US
Funding
Project-005UL1TR001430 · NCATS · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BAIR-MERRITT, MEGAN H, CENTER, DAVID M. · 2015 to 2024
$52.3MNew Jersey Alliance for Clinical Translational Science: NJ ACTSUL1TR003017 · NCATS · RUTGERS BIOMEDICAL/HEALTH SCIENCES-RBHS · PI PANETTIERI, REYNOLD ALEXANDER · 2019 to 2023
$28.9MGenetic Viral and Host Adaptations to Breach Species Barriers of HCVR01AI107301 · NIAID · PRINCETON UNIVERSITY · PI Thomas Pietschmann, Alexander Ploss · 2013 to 2026
$6.0MModeling immune impairments and pathogenesis in novel humanized mice for HBV-HIV co-infectionR01AI138797 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI PLOSS, ALEXANDER, SU, LISHAN · 2018 to 2022
$3.9MData-Driven Mathematical and Computational Modeling of Hepatitis D Infection and Treatment ResponseR01AI146917 · NIAID · LOYOLA UNIVERSITY CHICAGO · PI DAHARI, HAREL · 2020 to 2024
$3.5MMechanisms of hepatitis B virus cccDNA formationR01AI153236 · NIAID · PRINCETON UNIVERSITY · PI PLOSS, ALEXANDER · 2020 to 2024
$2.8MEngineering Humoral Immunity to Functionally Cure HIV InfectionDP2DA040254 · NIDA · MASSACHUSETTS GENERAL HOSPITAL · PI BALAZS, ALEJANDRO BENJAMIN · 2015 to 2015
$2.6MRole reversal of MAVS in bacterial sepsisR01HL141513 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BOSMANN, MARKUS · 2018 to 2022
$2.4MBacterial polyphosphates in sepsisR01AI153613 · NIAID · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BOSMANN, MARKUS · 2021 to 2024
$2.1MNew genetic models for C5a receptorsR01HL139641 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BOSMANN, MARKUS · 2018 to 2022
$2.1MIntegrative clustering of cells and samples using multi-modal single-cell dataR01LM013154 · NLM · BOSTON UNIVERSITY MEDICAL CAMPUS · PI CAMPBELL, JOSHUA D, YAJIMA, MASANAO · 2019 to 2021
$1.1MGenetic probing of residues involved in ebolavirus glycoprotein entryR21AI135517 · NIAID · BOSTON UNIVERSITY MEDICAL CAMPUS · PI CONNOR, JOHN H · 2018 to 2019
$454kNCATS NIH HHS UL1 TR001430NCATS NIH HHS UL1 TR003017NHLBI NIH HHS R01 HL139641NHLBI NIH HHS R01 HL141513NIAID NIH HHS K22 AI144050NIAID NIH HHS R01 AI107301NIAID NIH HHS R01 AI138797NIAID NIH HHS R01 AI146917NIAID NIH HHS R01 AI153236NIAID NIH HHS R01 AI153613NIAID NIH HHS R21 AI135517NIDA NIH HHS DP2 DA040254NIEHS NIH HHS R21 ES032882NIH HHS S10 OD026983NIH HHS S10 OD030269NLM NIH HHS R01 LM013154
Abstract
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.
Indexed as
COVID-19AnimalsDisease Models, AnimalHumansImmunity, InnateLungMacrophagesMiceSARS-CoV-2antiviral responsesCOVID-19CP: ImmunologyCP: Microbiologyhuman immune responses to SARS-CoV-2humanized micemacrophage responses to SARS-CoV-2mouse models of SARS-CoV-2pulmonary immune responses
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