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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Oct 23, 2021 |
| Title |
CCR2-dependent monocyte-derived cells restrict SARS-CoV-2 infection |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
SARS-CoV-2 has caused a historic pandemic of respiratory disease (COVID-19) and current evidence suggests severe disease is associated with dysregulated immunity within the respiratory tract1,2. 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-dependent infiltration of monocytes restricts viral burden in the lung. We find that a recently developed mouse-adapted MA-SARS-CoV-2 strain, as well as the emerging B.1.351 variant, trigger an inflammatory response in the lung characterized by expression of pro-inflammatory cytokines and interferon-stimulated genes. Using intravital antibody labeling, we demonstrate that MA-SARS-CoV-2 infection leads to increases in circulating monocytes and an influx of CD45+ cells into the lung parenchyma that is dominated by monocyte-derived cells. scRNA-seq analysis of lung homogenates identified a hyper-inflammatory monocyte profile. We utilize this model to demonstrate that mechanistically, CCR2 signaling promotes infiltration of classical monocytes into the lung and 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 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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| Overall design |
8 samples in total corresponding to different mice. 4 samples are from mock, control mice. 4 samples are from SARS-CoV-2 infected mice.
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| Contributor(s) |
Vanderheiden A, Suthar M, Thomas J, Kohlmeier J, Bosinger S |
| Citation(s) |
34749524 |
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| Submission date |
Oct 21, 2021 |
| Last update date |
Nov 18, 2021 |
| Contact name |
Mehul Suthar |
| Organization name |
Emory University School of Medicine
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| Department |
Department of Pediatrics
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| Street address |
2015 Uppergate Dr
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| City |
Atlanta |
| State/province |
GA |
| ZIP/Postal code |
30322 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (8)
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| Relations |
| BioProject |
PRJNA773499 |
| SRA |
SRP342598 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE186360_RAW.tar |
103.9 Mb |
(http)(custom) |
TAR (of MTX, TSV) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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