MIF is a common genetic determinant of COVID-19 symptomatic infection and severity

Genetic predisposition to coronavirus disease 2019 (COVID-19) may contribute to its morbidity and mortality. Because cytokines play an important role in multiple phases of infection, we examined whether commonly occurring, functional polymorphisms in macrophage migration inhibitory factor (MIF) are associated with COVID-19 infection or disease severity.This work was supported by National Institute of Health (NIH) [1R01-AR078334 (RB), 5R01-AI51306 (RB), R01-HL155948 (MS, RB), 1R01AG056728 (IK), T32AR07107 (JPY) and KL2 TR001862 (JJS)]; the European Commission (DB) – NextGenerationEU (Regulation EU 2020/2094) through CSIC's Global Health Platform (PTI Salud Global), and Junta de Castilla y León (Programa Estratégico Instituto de Biología y Genética Molecular (IBGM), Junta de Castilla y León (CCVC8485); and the National Natural Science Foundation of China [#81901669 (WF)].Peer reviewe

Differential regulation of macrophage activation by the MIF cytokine superfamily members MIF and MIF-2 in adipose tissue during endotoxemia

Sepsis is a leading cause of death worldwide and recent studies have shown white adipose tissue (WAT) to be an important regulator in septic conditions. In the present study, the role of the inflammatory cytokine macrophage migration inhibitory factor (MIF) and its structural homolog D-dopachrome tautomerase (D-DT/MIF-2) were investigated in WAT in a murine endotoxemia model. Both MIF and MIF-2 levels were increased in the peritoneal fluid of LPS-challenged wild-type mice, yet, in visceral WAT, the proteins were differentially regulated, with elevated MIF but downregulated MIF-2 expression in adipocytes. Mif gene deletion polarized adipose tissue macrophages (ATM) toward an anti-inflammatory phenotype while Mif-2 gene knockout drove ATMs toward a pro-inflammatory phenotype and Mif-deficiency was found to increase fibroblast viability. Additionally, we observed the same differential regulation of these two MIF family proteins in human adipose tissue in septic vs healthy patients. Taken together, these data suggest an inverse relationship between adipocyte MIF and MIF-2 expression during systemic inflammation, with the downregulation of MIF-2 in fat tissue potentially increasing pro-inflammatory macrophage polarization to further drive adipose inflammation