tetano
Editor, Senior Moderator
Immunity
. 2024 Sep 27:S1074-7613(24)00417-5.
doi: 10.1016/j.immuni.2024.08.018. Online ahead of print. Antiviral innate immune memory in alveolar macrophages following SARS-CoV-2 infection ameliorates secondary influenza A virus disease
Alexander Lercher[SUP] 1 [/SUP], Jin-Gyu Cheong[SUP] 2 [/SUP], Michael J Bale[SUP] 2 [/SUP], Chenyang Jiang[SUP] 3 [/SUP], Hans-Heinrich Hoffmann[SUP] 4 [/SUP], Alison W Ashbrook[SUP] 4 [/SUP], Tyler Lewy[SUP] 4 [/SUP], Yue S Yin[SUP] 4 [/SUP], Corrine Quirk[SUP] 4 [/SUP], Emma J DeGrace[SUP] 5 [/SUP], Luis Chiriboga[SUP] 6 [/SUP], Brad R Rosenberg[SUP] 5 [/SUP], Steven Z Josefowicz[SUP] 7 [/SUP], Charles M Rice[SUP] 8 [/SUP]
Affiliations
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.
Keywords: SARS-CoV-2; alveolar macrophages; epigenetic memory; immunology; influenza; innate immune memory; lung disease; respiratory virus; trained immunity; viral infection.
. 2024 Sep 27:S1074-7613(24)00417-5.
doi: 10.1016/j.immuni.2024.08.018. Online ahead of print. Antiviral innate immune memory in alveolar macrophages following SARS-CoV-2 infection ameliorates secondary influenza A virus disease
Alexander Lercher[SUP] 1 [/SUP], Jin-Gyu Cheong[SUP] 2 [/SUP], Michael J Bale[SUP] 2 [/SUP], Chenyang Jiang[SUP] 3 [/SUP], Hans-Heinrich Hoffmann[SUP] 4 [/SUP], Alison W Ashbrook[SUP] 4 [/SUP], Tyler Lewy[SUP] 4 [/SUP], Yue S Yin[SUP] 4 [/SUP], Corrine Quirk[SUP] 4 [/SUP], Emma J DeGrace[SUP] 5 [/SUP], Luis Chiriboga[SUP] 6 [/SUP], Brad R Rosenberg[SUP] 5 [/SUP], Steven Z Josefowicz[SUP] 7 [/SUP], Charles M Rice[SUP] 8 [/SUP]
Affiliations
- PMID: 39353439
- DOI: 10.1016/j.immuni.2024.08.018
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.
Keywords: SARS-CoV-2; alveolar macrophages; epigenetic memory; immunology; influenza; innate immune memory; lung disease; respiratory virus; trained immunity; viral infection.