At the Intersection Between SARS-CoV-2, Macrophages and the Adaptive Immune Response: A Key Role for Antibody-Dependent Pathogenesis But Not Enhancement of Infection in COVID-19
At the Intersection Between SARS-CoV-2, Macrophages and the Adaptive Immune Response: A Key Role for Antibody-Dependent Pathogenesis But Not Enhancement of Infection in COVID-19
Abstract Since entering the world stage in December of 2019, SARS-CoV-2 has impacted every corner of the globe with over 1.48 million deaths and caused untold economic damage. Infections in humans range from asymptomatic to severe disease associated with dysregulation of the immune system leading to the development of acute respiratory distress syndrome (ARDs). The distinct shift in peripheral monocyte activation and infiltration of these cells into the respiratory tract in ARDs patients suggests severe COVID-19 may largely result from damage to the respiratory epithelia by improperly activated macrophages. Here, we present evidence that dysregulation of the immune response in COVID-19 begins with activation of macrophages by non-neutralizing antibodies and induction of ACE2 expression, rendering these cells susceptible to killing by SARS-CoV-2. Death of macrophages occurs independently of viral replication and leads to the release of inflammatory mediators and modulation of the susceptibility of downstream epithelial cells to SARS-CoV-2.
Palmer Kenneth E.、Severson Wiliam E.、DeMarco Daniel R.、Pogue Gregory、Gabbard Jon、DeMarco Jennifer K.
Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville||Department of Microbiology and Immunology, University of Louisville||James Graham Brown Cancer Center, University of LouisvilleCenter for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of LouisvilleEurofins Microbiology LaboratoriesKentucky BioProcessing Inc.Center for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of LouisvilleCenter for Predictive Medicine for Biodefense and Emerging Infectious Diseases, University of Louisville||Department of Microbiology and Immunology, University of Louisville
基础医学微生物学
COVID-19SARS-CoV-2macrophageantibody-dependent enhancement
Palmer Kenneth E.,Severson Wiliam E.,DeMarco Daniel R.,Pogue Gregory,Gabbard Jon,DeMarco Jennifer K..At the Intersection Between SARS-CoV-2, Macrophages and the Adaptive Immune Response: A Key Role for Antibody-Dependent Pathogenesis But Not Enhancement of Infection in COVID-19[EB/OL].(2025-03-28)[2025-05-21].https://www.biorxiv.org/content/10.1101/2021.02.22.432407.点此复制
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