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Updated: Oct 14, 2025
08:41
Live Imaging and Quantification of Viral Infection in K18 hACE2 Transgenic Mice Using Reporter-Expressing Recombinant SARS-CoV-2
Published on: November 5, 2021
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CCR2 Signaling Restricts SARS-CoV-2 Infection
Abigail Vanderheiden1,2,3, Jeronay Thomas4,5, Allison L Soung6
1Center for Childhood Infections and Vaccines of Children's Healthcare of Atlanta, Department of Pediatrics, Emory Universitygrid.189967.8grid.471395.dgrid.189967.8grid.471395.dgrid.189967.8grid.471395.d School of Medicine, Atlanta, Georgia, USA.
Mbio
|November 9, 2021
Summary
Early CCR2 signaling and monocyte infiltration are crucial for controlling SARS-CoV-2 viral load in the lungs. This innate immune response helps restrict viral spread and manage inflammation during COVID-19.
Area of Science:
- Immunology
- Virology
- Respiratory Medicine
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, a pandemic disease often linked to respiratory tract immune dysregulation.
- Innate immune mechanisms protecting against severe COVID-19 remain incompletely understood.
Purpose of the Study:
- To characterize a mouse model of SARS-CoV-2 infection to define innate immune responses.
- To investigate the role of CCR2 signaling in controlling viral burden and inflammation during SARS-CoV-2 infection.
Main Methods:
- Development and utilization of a mouse-adapted SARS-CoV-2 (MA-SARS-CoV-2) strain.
- Intravital antibody labeling, single-cell RNA sequencing (scRNA-Seq), and flow cytometry.
- Analysis of gene expression for proinflammatory cytokines and interferon-stimulated genes.
Main Results:
- MA-SARS-CoV-2 infection induced lung inflammation with increased proinflammatory cytokines and interferon-stimulated genes.
- SARS-CoV-2 infection led to increased circulating monocytes and CD45+ cell influx into the lung, dominated by monocyte-derived cells.
- CCR2 signaling promoted classical monocyte infiltration and expansion of monocyte-derived cells, which were protective against viral load and dissemination.
Conclusions:
- A critical CCR2-monocyte axis promotes viral control and restricts inflammation in the respiratory tract during SARS-CoV-2 infection.
- Early CCR2-dependent monocyte infiltration is essential for limiting viral burden in the lungs.
- Monocyte-derived cells play a protective role in the lung parenchyma against SARS-CoV-2.
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