Recruitment of pulmonary intravascular macrophages in SARS-CoV-2 infected hamsters
Carolina Rego Rodrigues1, Gurpreet Kaur Aulakh2, Andrea Kroeker3
1Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, Canada.
Abstract:
The mechanisms by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes severe lung inflammation and mortality remain unclear. While the role of alveolar macrophages in COVID-19 is known, data on pulmonary intravascular macrophages (PIMs) is lacking. PIMs are key inflammatory cells present in species like cattle and pigs. Though constitutively absent in humans and rodents, their recruitment in rodents triggers exaggerated inflammation. We investigated the recruitment of PIMs and other immune cells, using immunofluorescence, hematoxylin and eosin (H&E) staining, and immunogold labeling in a hamster model of SARS-CoV-2 infection. Syrian golden hamsters were divided into 6 groups: uninfected control, unvaccinated-infected at 2-, 5-, and 14-days post infection (dpi) and vaccinated-infected at 5- and 14-dpi. Lung tissues were analyzed for neutrophils (myeloperoxidase), monocytes/macrophages (CCR2, CX3CR1), macrophages (IBA-1), and T cells (CD3). Septal macrophages increased at 2-, 5-, and 14-dpi in infected animals vs. control. CX3CR1 + cells decreased at 14-dpi in unvaccinated animals, but CX3CR1/CCR2 double positive cells were higher at 5-dpi, indicating a pro-inflammatory macrophage phenotype. PIMs were confirmed by transmission electron microscopy. These are the first data showing recruitment of pro-inflammatory PIMs in SARS-CoV-2 infected lungs.
Insights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection triggers the recruitment of pro-inflammatory pulmonary intravascular macrophages (PIMs) in a hamster model. This study provides the first evidence of PIMs contributing to lung inflammation during SARS-CoV-2 infection.
Area of Science:
- Immunology
- Pathology
- Virology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes significant lung inflammation and mortality.
- Alveolar macrophages are implicated in COVID-19 pathogenesis, but pulmonary intravascular macrophages (PIMs) role is unknown.
- PIMs are inflammatory cells found in livestock, and their recruitment in rodents exacerbates inflammation.
Purpose of the Study:
- To investigate the recruitment of pulmonary intravascular macrophages (PIMs) and other immune cells in a hamster model of SARS-CoV-2 infection.
- To characterize the inflammatory response in the lungs of infected hamsters.
Main Methods:
- Utilized a Syrian golden hamster model infected with SARS-CoV-2.
- Employed immunofluorescence, hematoxylin and eosin (H&E) staining, and immunogold labeling to analyze lung tissues.
- Quantified neutrophils, monocytes/macrophages, macrophages, and T cells, and confirmed PIMs via transmission electron microscopy.
Main Results:
- Increased septal macrophages observed at 2, 5, and 14 days post-infection (dpi) in infected hamsters compared to controls.
- A shift towards a pro-inflammatory macrophage phenotype was indicated by increased CX3CR1/CCR2 double-positive cells at 5 dpi.
- Confirmed the recruitment of pulmonary intravascular macrophages (PIMs) in SARS-CoV-2 infected hamster lungs.
Conclusions:
- This study presents the first evidence of pulmonary intravascular macrophage (PIM) recruitment during SARS-CoV-2 infection.
- The findings suggest that PIMs contribute to the pro-inflammatory response in the lungs following SARS-CoV-2 infection.
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