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