Unveiled the role of the transcription factor MAFB in the macrophage response to SARS-CoV-2 and its regulation in severe COVID-19

A paper published in the journal JCI Insights by Dr. Ángeles Domínguez-Soto, a researcher in the group led by Dr. Ángel Corbí at the Centro de Investigaciones Biológicas Margarita Salas (CSIC), delves into the role of the transcription factor MAFB in the response of monocyte-derived macrophages to SARS-CoV-2.

Using both genetic and pharmacological approaches on primary cultures of monocyte-derived macrophages, Simón-Fuentes et al. demonstrate that MAFB is key in regulating the expression of genes defining lung pathogenic macrophages in severe COVID-19.

The study reveals that exposure to SARS-CoV-2 increases the expression of MAFB and the genes it regulates in monocyte-derived macrophages, leading to increased production of profibrotic and neutrophil-attracting factors. Thus, macrophages exposed to the virus adopt a profibrotic and proinflammatory profile.

In addition, researchers have shown that MAFB is essential for the expression of several soluble factors that predict the severity and prognosis of COVID-19, including CCL18, CCL2, CXCL10, CXCL13, and SPP1. Therefore, MAFB not only determines the transcriptome and functions of monocyte-derived macrophage subsets involved in the pulmonary pathogenesis of severe COVID-19 but also regulates the expression of biomarkers that may be useful for assessing disease severity.

The work opens the possibility of using macrophage reprogramming as a therapeutic strategy in the context of severe COVID-19, as well as the role of MAFB in those patients suffering from persistent COVID, to understand the underlying mechanisms of this prolonged condition and contribute to its management.

This paper is the result of a collaboration of the CIB Margarita Salas with the Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), the Instituto de Investigación Hospital Universitario 12 de Octubre (imas12), the University Hospital La Princesa and Research Institute, and the Institute of Biomedicine of Seville (IBiS).

Reference: MAFB shapes human monocyte–derived macrophage response to SARS-CoV-2 and controls severe COVID-19 biomarker expression. Miriam Simón-Fuentes, Israel Ríos, Cristina Herrero, Fátima Lasala, Nuria Labiod, Joanna Luczkowiak, Emilia Roy-Vallejo, Sara Fernández de Córdoba-Oñate, Pablo Delgado-Wicke, Matilde Bustos, Elena Fernández-Ruiz, María Colmenares, Amaya Puig-Kröger, Rafael Delgado, Miguel A. Vega, Ángel L. Corbí, and Ángeles Domínguez-Soto (2023) JCI Insight. 2023;8(24):e172862. https://doi.org/10.1172/jci.insight.172862.