Reference - Detail
RRC ID | 81783 |
---|---|
Author | Lercher A, Cheong JG, Bale MJ, Jiang C, Hoffmann HH, Ashbrook AW, Lewy T, Yin YS, Quirk C, DeGrace EJ, Chiriboga L, Rosenberg BR, Josefowicz SZ, Rice CM. |
Title | Antiviral innate immune memory in alveolar macrophages following SARS-CoV-2 infection ameliorates secondary influenza A virus disease. |
Journal | Immunity |
Abstract |
Pathogen encounter can result in epigenetic remodeling that shapes disease caused by heterologous pathogens. Here, we examined innate immune memory in the context of commonly circulating respiratory viruses. Single-cell analyses of airway-resident immune cells in a disease-relevant murine model of SARS-CoV-2 recovery revealed epigenetic reprogramming in alveolar macrophages following infection. Post-COVID-19 human monocytes exhibited similar epigenetic signatures. In airway-resident macrophages, past SARS-CoV-2 infection increased activity of type I interferon (IFN-I)-related transcription factors and epigenetic poising of antiviral genes. Viral pattern recognition and canonical IFN-I signaling were required for the establishment of this innate immune memory and augmented secondary antiviral responses. Antiviral innate immune memory mounted by airway-resident macrophages post-SARS-CoV-2 was necessary and sufficient to ameliorate secondary disease caused by influenza A virus and curtailed hyperinflammatory dysregulation and mortality. Our findings provide insights into antiviral innate immune memory in the airway that may facilitate the development of broadly effective therapeutic strategies. |
Published | 2024-9-27 |
DOI | 10.1016/j.immuni.2024.08.018 |
PII | S1074-7613(24)00417-5 |
PMID | 39353439 |
Resource | |
Mice | RBRC00916 |