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

Caution: Preprints are preliminary reports of work that have not been certified by peer review. They should not be relied on to guide clinical practice or health-related behavior and should not be reported in news media as established information.

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Published

November 2023

Journal

bioRxiv

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.

Authors

Alexander Lercher, Jin-Gyu Cheong, Chenyang Jiang, Hans-Heinrich Hoffmann, Alison W Ashbrook, Yue S Yin, Corrine Quirk, Emma J DeGrace, Luis Chiriboga, Brad R Rosenberg, Steven Z Josefowicz, Charles M Rice

Keywords

Not available