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

• Main Authors: Miguel A. Vega, Miriam Simón-Fuentes, Arturo González de la Aleja, Concha Nieto, María Colmenares, Cristina Herrero, Ángeles Domínguez-Soto, Ángel L. Corbí
• Format: Article
• Language: English
• Published: Frontiers Media S.A. 2020-11-01
• Series: Frontiers in Immunology
• Subjects: macrophage; innate immunity; COVID-19; MAFB; MAF
• Online Access: https://www.frontiersin.org/articles/10.3389/fimmu.2020.603507/full

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.