IL-1β-driven NF-κB transcription of ACE2 as a Mechanism of Macrophage Infection by SARS-CoV-2
2024

How Macrophages Get Infected by SARS-CoV-2

publication Evidence: moderate

Author Information

Author(s): Lee Cadence, Khan Rachel, Mantsounga Chris S., Sharma Sheila, Pierce Julia, Amelotte Elizabeth, Butler Celia A., Farinha Andrew, Parry Crystal, Caballero Olivya, Morrison Jeremi A., Uppuluri Saketh, Whyte Jeffrey J., Kennedy Joshua L., Zhang Xuming, Choudhary Gaurav, Olson Rachel M., Morrison Alan R.

Primary Institution: Ocean State Research Institute, Inc.

Hypothesis

Can macrophages be infected by SARS-CoV-2 and what mechanisms regulate ACE2 expression in these cells?

Conclusion

The study found that macrophages can be infected by SARS-CoV-2, and this infection is linked to the upregulation of ACE2 driven by IL-1β signaling.

Supporting Evidence

  • Macrophages in the hACE2 mouse model showed evidence of viral replication after SARS-CoV-2 infection.
  • Infected hACE2 mice exhibited a unique inflammatory signature compared to other mouse models.
  • IL-1β was found to drive the upregulation of ACE2 in macrophages, making them more susceptible to infection.

Takeaway

This research shows that a type of immune cell called macrophages can get infected by the virus that causes COVID-19, and this happens because of a special signal in the body that makes a receptor called ACE2 more available.

Methodology

The study used a humanized ACE2 mouse model to investigate the infection of macrophages by SARS-CoV-2 and the associated immune responses.

Limitations

The study did not explore the role of macrophage infection in disease pathology or viral clearance, and further research is needed to validate findings in human specimens.

Digital Object Identifier (DOI)

10.1101/2024.12.24.630260

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