Soluble mannose receptor induces proinflammatory macrophage activation and metaflammation.
Animal Feed
Animals
Cells, Cultured
Cytokines
/ genetics
Diet, High-Fat
Gastrointestinal Microbiome
Gene Expression Regulation
/ drug effects
Inflammation
Macrophage Activation
/ drug effects
Macrophages
/ metabolism
Male
Mannose Receptor
/ chemistry
Membrane Proteins
/ pharmacology
Mice
Mice, Knockout
Random Allocation
immunometabolism
macrophage
mannose receptor
metaflammation
obesity
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
03 08 2021
03 08 2021
Historique:
entrez:
30
7
2021
pubmed:
31
7
2021
medline:
15
12
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34326259
pii: 2103304118
doi: 10.1073/pnas.2103304118
pmc: PMC8346872
pii:
doi:
Substances chimiques
Cytokines
0
Fcmr protein, mouse
0
Mannose Receptor
0
Membrane Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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