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SARS-CoV-2 evades immune detection in alveolar macrophages
Louise Dalskov1, Michelle Møhlenberg1, Jacob Thyrsted2
1Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.
Abstract:
Respiratory infections, like the current COVID-19 pandemic, target epithelial cells in the respiratory tract. Alveolar macrophages (AMs) are tissue-resident macrophages located within the lung. They play a key role in the early phases of an immune response to respiratory viruses. AMs are likely the first immune cells to encounter SARS-CoV-2 during an infection, and their reaction to the virus will have a profound impact on the outcome of the infection. Interferons (IFNs) are antiviral cytokines and among the first cytokines produced upon viral infection. In this study, AMs from non-infectious donors are challenged with SARS-CoV-2. We demonstrate that challenged AMs are incapable of sensing SARS-CoV-2 and of producing an IFN response in contrast to other respiratory viruses, like influenza A virus and Sendai virus, which trigger a robust IFN response. The absence of IFN production in AMs upon challenge with SARS-CoV-2 could explain the initial asymptotic phase observed during COVID-19 and argues against AMs being the sources of pro-inflammatory cytokines later during infection.
Insights
Alveolar macrophages (AMs) fail to detect SARS-CoV-2, unlike other viruses, hindering early antiviral interferon production. This impaired immune response in AMs may explain COVID-19’s initial asymptomatic phase.
Area of Science:
- Immunology
- Virology
- Respiratory Medicine
Background:
- Respiratory infections, including COVID-19, primarily affect lung epithelial cells.
- Alveolar macrophages (AMs) are crucial immune cells in the lungs, initiating early antiviral responses.
- AMs are likely the first responders to SARS-CoV-2, significantly influencing infection outcomes.
Purpose of the Study:
- To investigate the response of alveolar macrophages (AMs) to SARS-CoV-2.
- To determine if AMs can sense SARS-CoV-2 and initiate an interferon (IFN) response.
- To compare AM response to SARS-CoV-2 with responses to other respiratory viruses.
Main Methods:
- AMs from healthy donors were exposed to SARS-CoV-2 in vitro.
- The production of interferons (IFNs) by AMs was measured after viral challenge.
- IFN responses were compared between SARS-CoV-2, influenza A virus, and Sendai virus challenges.
Main Results:
- AMs challenged with SARS-CoV-2 did not produce interferons (IFNs).
- In contrast, influenza A virus and Sendai virus triggered a strong IFN response in AMs.
- This indicates a failure of AMs to sense and respond to SARS-CoV-2 with IFN production.
Conclusions:
- The inability of AMs to produce IFNs upon SARS-CoV-2 exposure may explain the initial asymptomatic phase of COVID-19.
- This finding suggests AMs are not the primary source of pro-inflammatory cytokines later in the infection.
- Understanding this early immune evasion is critical for developing effective COVID-19 therapies.
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