Antiviral innate immune memory in alveolar macrophages following SARS-CoV-2 infection

  1. Alexander Lercher
  2. Jin-Gyu Cheong
  3. Chenyang Jiang
  4. Hans-Heinrich Hoffmann
  5. Alison W. Ashbrook
  6. Yue S. Yin
  7. Corrine Quirk
  8. Emma J. DeGrace
  9. Luis Chiriboga
  10. Brad R. Rosenberg
  11. Steven Z. Josefowicz
  12. Charles M. Rice

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Abstract

Pathogen encounter results in long-lasting epigenetic imprinting that shapes diseases caused by heterologous pathogens. The breadth of this innate immune memory is of particular interest in the context of respiratory pathogens with increased pandemic potential and wide-ranging impact on global health. Here, we investigated epigenetic imprinting across cell lineages in a disease relevant murine model of SARS-CoV-2 recovery. Past SARS-CoV-2 infection resulted in increased chromatin accessibility of type I interferon (IFN-I) related transcription factors in airway-resident macrophages. Mechanistically, establishment of this innate immune memory required viral pattern recognition and canonical IFN-I signaling and augmented secondary antiviral responses. Past SARS-CoV-2 infection ameliorated disease caused by the heterologous respiratory pathogen influenza A virus. Insights into innate immune memory and how it affects subsequent infections with heterologous pathogens to influence disease pathology could facilitate the development of broadly effective therapeutic strategies.

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  1. PREreview

    This Zenodo record is a permanently preserved version of a Structured PREreview. You can view the complete PREreview at https://prereview.org/reviews/10278857.

    Does the introduction explain the objective of the research presented in the preprint? Yes
    Are the methods well-suited for this research? Highly appropriate
    Are the conclusions supported by the data? Highly supported
    Are the data presentations, including visualizations, well-suited to represent the data? Highly appropriate and clear
    How clearly do the authors discuss, explain, and interpret their findings and potential next steps for the research? Very clearly
    Is the preprint likely to advance academic knowledge? Highly likely
    Would it benefit from language editing? No
    Would you recommend this preprint to others? Yes, it's of high quality
    Is it ready for attention from an editor, publisher or broader audience? Yes, as it is

    Competing interests

    The author declares that they have no competing interests.

  2. Version published to 10.1101/2023.11.24.568354v1 on bioRxiv