MAFB and MAF Transcription Factors as Macrophage Checkpoints for COVID-19 Severity

Front Immunol. 2020 Nov 18;11:603507. doi: 10.3389/fimmu.2020.603507. eCollection 2020.


Defective IFN production and exacerbated inflammatory and pro-fibrotic responses are hallmarks of SARS-CoV-2 infection in severe COVID-19. Based on these hallmarks, and considering the pivotal role of macrophages in COVID-19 pathogenesis, we hypothesize that the transcription factors MAFB and MAF critically contribute to COVID-19 progression by shaping the response of macrophages to SARS-CoV-2. Our proposal stems from the recent identification of pathogenic lung macrophage subsets in severe COVID-19, and takes into consideration the previously reported ability of MAFB to dampen IFN type I production, as well as the critical role of MAFB and MAF in the acquisition and maintenance of the transcriptional signature of M-CSF-conditioned human macrophages. Solid evidences are presented that link overexpression of MAFB and silencing of MAF expression with clinical and biological features of severe COVID-19. As a whole, we propose that a high MAFB/MAF expression ratio in lung macrophages could serve as an accurate diagnostic tool for COVID-19 progression. Indeed, reversing the macrophage MAFB/MAF expression ratio might impair the exacerbated inflammatory and profibrotic responses, and restore the defective IFN type I production, thus becoming a potential strategy to limit severity of COVID-19.

Keywords: COVID-19; MAF; MAFB; innate immunity; macrophage.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • COVID-19 / genetics
  • COVID-19 / immunology*
  • COVID-19 / virology
  • Gene Expression Profiling / methods
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / immunology
  • Host-Pathogen Interactions / genetics
  • Host-Pathogen Interactions / immunology
  • Humans
  • Macrophages / immunology*
  • Macrophages / metabolism
  • Maf Transcription Factors / genetics
  • Maf Transcription Factors / immunology*
  • Maf Transcription Factors / metabolism
  • MafB Transcription Factor / genetics
  • MafB Transcription Factor / immunology*
  • MafB Transcription Factor / metabolism
  • SARS-CoV-2 / immunology*
  • SARS-CoV-2 / physiology
  • Severity of Illness Index


  • MAFB protein, human
  • Maf Transcription Factors
  • MafB Transcription Factor