Soluble mannose receptor induces proinflammatory macrophage activation and metaflammation.

Autor:	Embgenbroich M; Cellular Immunology, Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany., van der Zande HJP; Department of Parasitology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands., Hussaarts L; Department of Parasitology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands., Schulte-Schrepping J; Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany., Pelgrom LR; Department of Parasitology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands., García-Tardón N; Department of Parasitology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands., Schlautmann L; Cellular Immunology, Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany., Stoetzel I; Cellular Immunology, Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany., Händler K; Platform for Single-Cell Genomics and Epigenomics, German Center for Neurodegenerative Diseases and University of Bonn, 53115 Bonn, Germany., Lambooij JM; Department of Parasitology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands., Zawistowska-Deniziak A; Department of Parasitology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands.; Witold Stefański Institute of Parasitology, Polish Academy of Sciences, 00-818 Warsaw, Poland., Hoving L; Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., de Ruiter K; Department of Parasitology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands., Wijngaarden MA; Department of Internal Medicine, Section Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Pijl H; Department of Internal Medicine, Section Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Willems van Dijk K; Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.; Department of Internal Medicine, Section Endocrinology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Everts B; Department of Parasitology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands., van Harmelen V; Department of Human Genetics, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands., Yazdanbakhsh M; Department of Parasitology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands., Schultze JL; Genomics and Immunoregulation, Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany.; Platform for Single-Cell Genomics and Epigenomics, German Center for Neurodegenerative Diseases and University of Bonn, 53115 Bonn, Germany., Guigas B; Department of Parasitology, Leiden University Medical Center, 2333ZA Leiden, The Netherlands; b.g.a.guigas@lumc.nl burgdorf@uni-bonn.de., Burgdorf S; Cellular Immunology, Life and Medical Sciences Institute, University of Bonn, 53115 Bonn, Germany; b.g.a.guigas@lumc.nl burgdorf@uni-bonn.de.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 Aug 03; Vol. 118 (31).
DOI:	10.1073/pnas.2103304118
Abstrakt:	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 (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-κB-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. Competing Interests: The authors declare no competing interest.
Databáze:	MEDLINE
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