The mannose receptor is a member of the C-type lectin (CLEC) family, which can bind and internalize a variety of endogenous and pathogen-associated ligands. Because of these properties, its role in... Show moreThe mannose receptor is a member of the C-type lectin (CLEC) family, which can bind and internalize a variety of endogenous and pathogen-associated ligands. Because of these properties, its role in endocytosis as well as antigen processing and presentation has been studied intensively. Recently, it became clear that the mannose receptor can directly influence the activation of various immune cells. Cell-bound mannose receptor expressed by antigen-presenting cells was indeed shown to drive activated T cells towards a tolerogenic phenotype. On the other hand, serum concentrations of a soluble form of the mannose receptor have been reported to be increased in patients suffering from a variety of inflammatory diseases and to correlate with severity of disease. Interestingly, we recently demonstrated that the soluble mannose receptor directly promotes macrophage proinflammatory activation and trigger metaflammation. In this review, we highlight the role of the mannose receptor and other CLECs in regulating the activation of immune cells and in shaping inflammatory responses. Show less
Embgenbroich, M.; Zande, H.J.P. van der; Hussaarts, L.; Schulte-Schrepping, J.; Pelgrom, L.R.; Garcia-Tardon, N.; ... ; Burgdorf, S. 2021
Proinflammatory activation of macrophages in metabolic tissues is critically important in the induction of obesity-induced metaflammation. Here, we demonstrate that the soluble mannose receptor ... Show moreProinflammatory activation of macrophages in metabolic tissues is critically important in the induction of obesity-induced metaflammation. Here, we demonstrate that the soluble mannose receptor (sMR) plays a direct functional role in both macrophage activation and metaflammation. We show that sMR binds CD45 on macrophages and inhibits its phosphatase activity, leading to an Src/Akt/ NF-kappa B-mediated cellular reprogramming toward an inflammatory phenotype both in vitro and in vivo. Remarkably, increased serum sMR levels were observed in obese mice and humans and directly correlated with body weight. Importantly, enhanced sMR levels increase serum proinflammatory cytokines, activate tissue macrophages, and promote insulin resistance. Altogether, our results reveal sMR as regulator of proinflammatory macrophage activation, which could constitute a therapeutic target for metaflammation and other hyperinflammatory diseases. Show less
