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Author Notes:

Mehul S. Suthar, mehul.s.suthar@emory

A.V. and M.S.S. contributed to the acquisition, analysis, and interpretation of the data; the conception and design of the work; and writing of the manuscript. J.T. and J.E.K. contributed to the analysis and interpretation of the data and writing of the manuscript. A.L.S. contributed to the acquisition, analysis, and interpretation of the data and writing of the manuscript. M.E.D.-G., K.F., and F.J. contributed to the acquisition and analysis of the data. R.S.K. contributed to the analysis and interpretation of the data and conception and design of the work. S.E.B., D.A.C., K.P., A.G., P.-Y.S., and V.D.M. contributed to the interpretation of the data and conception and design of the work.

We thank Andy Pekosz for the B.1.351 variant. We also thank Eli Boritz and Danny Douek for sequencing and analysis of the B.1.351 variant (NIAID/NIH, Atlanta, GA).


Research Funding:

This work was supported in part by grants (P51 OD011132 and R56 AI147623 to Emory University) from the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH); an Emory Executive Vice President for Health Affairs Synergy Fund award; the Pediatric Research Alliance Center for Childhood Infections and Vaccines and Children’s Healthcare of Atlanta; the Emory-UGA Center of Excellence for Influenza Research and Surveillance, HHSN272201400004C; and a Woodruff Health Sciences Center 2020 COVID-19 CURE award. J.T. is supported by T32 AI074492. Next-generation sequencing services were provided by the Yerkes NHP Genomics Core, which is supported in part by NIH grant P51 OD 011132, and the data were acquired on a NovaSeq 6000 platform funded by NIH grant S10 OD 026799.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Microbiology
  • lung inflammation
  • monocytes
  • SARS-CoV-2
  • innate immunity
  • mouse model
  • MILD
  • LIFE

CCR2 Signaling Restricts SARS-CoV-2 Infection

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Journal Title:



Volume 12, Number 6


, Pages e0274921-e0274921

Type of Work:

Article | Final Publisher PDF


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a historic pandemic of respiratory disease (coronavirus disease 2019 [COVID-19]), and current evidence suggests that severe disease is associated with dysregulated immunity within the respiratory tract. However, the innate immune mechanisms that mediate protection during COVID-19 are not well defined. Here, we characterize a mouse model of SARS-CoV-2 infection and find that early CCR2 signaling restricts the viral burden in the lung. We find that a recently developed mouse-adapted SARS-CoV-2 (MA-SARSCoV- 2) strain as well as the emerging B.1.351 variant trigger an inflammatory response in the lung characterized by the expression of proinflammatory cytokines and interferon- stimulated genes. Using intravital antibody labeling, we demonstrate that MASARS- CoV-2 infection leads to increases in circulating monocytes and an influx of CD451 cells into the lung parenchyma that is dominated by monocyte-derived cells. Single-cell RNA sequencing (scRNA-Seq) analysis of lung homogenates identified a hyperinflammatory monocyte profile. We utilize this model to demonstrate that mechanistically, CCR2 signaling promotes the infiltration of classical monocytes into the lung and the expansion of monocyte-derived cells. Parenchymal monocyte-derived cells appear to play a protective role against MA-SARS-CoV-2, as mice lacking CCR2 showed higher viral loads in the lungs, increased lung viral dissemination, and elevated inflammatory cytokine responses. These studies have identified a potential CCR2-monocyte axis that is critical for promoting viral control and restricting inflammation within the respiratory tract during SARS-CoV-2 infection.

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This is a work of the U.S. Government and is not subject to copyright protection in the United States. Foreign copyrights may apply.

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