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

Vega, Miguel A.; Simón-Fuentes, Miriam; Aleja, Arturo González de la; Nieto, Concha; Colmenares, Marı́a; Herrero, Cristina; Domínguez-Soto, Ángeles; Corbí, Ángel L.

doi:10.3389/fimmu.2020.603507

Cited by 27 publications

(33 citation statements)

References 57 publications

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“…MafB is also a key regulator involved in functional programing of macrophages in the context of tissue imprinting (43), lipid/cholesterol-rich environments or wound healing (44). Of note, the balance between MAF and MafB in alveolar macrophages could shape the response to SARS-CoV2 (45).…”

Section: Discussionmentioning

confidence: 99%

Functional reprogramming of monocytes in acute and convalescent severe COVID-19 patients

Brauns

Azouz

Grimaldi

et al. 2021

Preprint

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Severe COVID-19 disease is associated with dysregulation of the myeloid compartment during acute infection. Survivors frequently experience long-lasting sequelae but little is known about the eventual persistence of this immune alteration. Herein, we evaluated Toll-like receptor-induced cytokine responses in a cohort of mild to critical patients during acute or convalescent phases (n=97). In the acute phase, we observed impaired cytokine production by monocytes in the most severe patients. This capacity was globally restored in convalescent patients. Yet, we observed increased responsiveness to TLR1/2 ligation in patients that recovered from severe disease, indicating that these cells display distinct functional properties at the different stages of the disease. We identified a specific transcriptomic and epigenomic state in monocytes from acute severe patients that can account for their functional refractoriness. The molecular profile of monocytes from recovering patients was distinct and characterized by increased chromatin accessibility at AP-1 and MAF loci. These results demonstrate that severe COVID-19 infection has a profound impact on the differentiation status and function of circulating monocytes both during the acute and the convalescent phases in a completely distinct manner. This could have important implications for our understanding of short and long-term COVID19-related morbidity.

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Section: Discussionmentioning

confidence: 99%

Functional reprogramming of monocytes in acute and convalescent severe COVID-19 patients

Brauns

Azouz

Grimaldi

et al. 2021

Preprint

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“…In any case, an increasing viral load results in continuously elevating numbers of activated macrophages and sustained hyperinflammation—known as the second cytokine wave—with severe tissue damage and life-threatening consequences [reviewed in ( 18 )]. Very recently, several molecules associated with macrophages functions, such as the plasma levels of long pentraxin 3 (PTX3), as well as, the ratio of the transcription factors MAFB/MAF have been suggested as potential prognostic indicators of disease progression and severity ( 24 , 25 ). Of note, it has been speculated that the differences in disease severity between adults and children might be explained by the potential age-heterogeneity of macrophage populations in lungs and other organs during development ( 26 ) as well as, by the potential development of memory macrophages upon frequent adjuvant-involving vaccination during childhood ( 27 ).…”

Section: Macrophages As Key Orchestrators Of the Inflammatory Milieu mentioning

confidence: 99%

Specialized Pro-Resolving Mediators as Potential Regulators of Inflammatory Macrophage Responses in COVID-19

2021

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The recent outbreak of SARS-CoV2 has emerged as one of the biggest pandemics of our century, with outrageous health, social and economic consequences globally. Macrophages may lay in the center of COVID-19 pathogenesis and lethality and treatment of the macrophage-induced cytokine storm has emerged as essential. Specialized pro-resolving mediators (SPMs) hold strong therapeutic potentials in the management of COVID-19 as they can regulate macrophage infiltration and cytokine production but also promote a pro-resolving macrophage phenotype. In this review, we discuss the homeostatic functions of SPMs acting directly on macrophages on various levels, towards the resolution of inflammation. Moreover, we address the molecular events that link the lipid mediators with COVID-19 severity and discuss the clinical potentials of SPMs in COVID-19 immunotherapeutics.

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“…The issue of appropriate timing for therapeutic modulation of viral pulmonary inflammatory responses is a matter of debate. It may be possible that altering the FCN1 + , SPP1 + /FABP4 + AM ratio in favor of maintaining a high level of FABP4 + cells may prevent the overwhelming proinflammatory response encountered at the later stages of COVID-19 and other RVIs ( Vega et al, 2020 ).…”

Section: Discussion and Future Directionsmentioning

confidence: 99%

GM-CSF: Orchestrating the Pulmonary Response to Infection

McCormick

Hejal

Leal³

et al. 2022

Front. Pharmacol.

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This review summarizes the structure and function of the alveolar unit, comprised of alveolar macrophage and epithelial cell types that work in tandem to respond to infection. Granulocyte-macrophage colony-stimulating factor (GM-CSF) helps to maintain the alveolar epithelium and pulmonary immune system under physiological conditions and plays a critical role in restoring homeostasis under pathologic conditions, including infection. Given the emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and global spread of coronavirus disease 2019 (COVID-19), with subsequent acute respiratory distress syndrome, understanding basic lung physiology in infectious diseases is especially warranted. This review summarizes clinical and preclinical data for GM-CSF in respiratory infections, and the rationale for sargramostim (yeast-derived recombinant human [rhu] GM-CSF) as adjunctive treatment for COVID-19 and other pulmonary infectious diseases.

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

Cited by 27 publications

References 57 publications

Functional reprogramming of monocytes in acute and convalescent severe COVID-19 patients

Functional reprogramming of monocytes in acute and convalescent severe COVID-19 patients

Specialized Pro-Resolving Mediators as Potential Regulators of Inflammatory Macrophage Responses in COVID-19

GM-CSF: Orchestrating the Pulmonary Response to Infection

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