Journal
FRONTIERS IN IMMUNOLOGY
Volume 11, Issue -, Pages -Publisher
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2020.603507
Keywords
macrophage; innate immunity; COVID-19; MAFB; MAF
Categories
Funding
- Consejo Superior de Investigaciones Cientificas [202020E228]
- Ministerio de Economia y Competitividad [SAF2017-83785-R]
- Fundacion La Marato/TV3 [201619.31]
- Red de Investigacion en Enfermedades Reumaticas (RIER) from Fundacion La Marato/TV3 [RD16/0012/0007]
- Instituto de Salud Carlos III
- European Regional Development Fund A way to achieve Europe (ERDF)
- CSIC Open Access Publication Support Initiative through its Unit of Information Resources for Research (URICI)
- AYUDAS FUNDACION BBVA A EQUIPOS DE INVESTIGACION CIENTIFICA SARS-CoV-2 y COVID-19
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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.
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