Distinct uptake, amplification, and release of SARS-CoV-2 by M1 and M2 alveolar macrophages.
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ABSTRACT:
SUBMITTER: Lv J
PROVIDER: S-EPMC8043100 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
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Project description:Respiratory infections, like the current pandemic SARS-CoV-2 virus, target the epithelial cells in the respiratory tract. However, alveolar macrophages (AMs) are tissue-resident macrophages located within the alveoli of the lung and they play a key role in the early phases of an immune response to respiratory infections. We expect that AMs are the first immune cells to encounter the SARS-CoV-2 and therefore their reaction to SARS-CoV-2 infection will have a profound impact upon the outcome of the infection. Interferons (IFNs) are antiviral cytokines and the first cytokine produced upon viral infection. Here, we challenge AMs with SARS-CoV-2 and to our surprise find that the AMs are incapable of recognising SARS-CoV-2 and produce IFN. This is in contrast to respiratory pathogens, such as influenza A virus and Sendai virus. Callenge of AMs with those viruses resulted in a robust IFN response. The absence of IFN production by AMs upon challenge could explain the initial asymptotic phase of SARS-CoV-2 infections and argues against the AMs as the source of proinflamatory cytokines later in infection.
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