Devêvre Estelle F, Renovato-Martins Mariana, Clément Karine, Sautès-Fridman Catherine, Cremer Isabelle, Poitou Christine
INSERM, Unité Mixte de Recherche 1138, Team 13, Centre de Recherches des Cordeliers, F-75006 Paris, France; INSERM, U1166, Nutriomic Team 6, F-75006 Paris, France; Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, F-75013 Paris, France; Université Paris Descartes, F-75006 Paris, France; Centre d'Imagerie Cellulaire et de Cytométrie, Centre de Recherche des Cordeliers, Unité Mixte de Recherche 1138, F-75006 Paris, France;
INSERM, Unité Mixte de Recherche 1138, Team 13, Centre de Recherches des Cordeliers, F-75006 Paris, France; INSERM, U1166, Nutriomic Team 6, F-75006 Paris, France; Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, F-75013 Paris, France; Université Paris Descartes, F-75006 Paris, France;
J Immunol. 2015 Apr 15;194(8):3917-23. doi: 10.4049/jimmunol.1402655. Epub 2015 Mar 18.
Three subpopulations of circulating monocytes have been described: CD14(2+)CD16(-) (classical monocytes [CM]), CD14(2+)CD16(+) (intermediate monocytes [IM]), and CD14(+)CD16(2+) (nonclassical monocytes [NCM]). We previously showed that obesity is associated with an increased proportion of IM and NCM. Our objective is to decipher the migratory and inflammatory functions of each monocyte subset in obesity-related low-grade inflammation. Twenty-six healthy, normal-weight and nondiabetic volunteers (C) and 40 obese nondiabetic (Ob) individuals were included in this study. We explored the gene expression profile of 18 inflammatory genes in each subset of C and Ob subjects and measured protein expression of the upregulated genes. We then tested their functional response to TLR signaling in both groups. We showed an increased expression of CX3CR1 in all monocyte subpopulations and of CCR2 and CCR5 in CM and IM in the Ob group. We found negative correlation between CCR2 and CX3CR1 expressions and high-density lipoprotein-cholesterol, whereas CCR5 expression was positively linked to obesity-related metabolic traits. Production of inflammatory proteins upon bacterial LPS and viral ssRNA stimulation was higher in CM and NCM of the Ob group compared with the C group. Our work highlights an enhanced inflammatory phenotype of monocytes with a higher response to TLR4 and TLR8 stimulations in obesity. Moreover, it suggests an increased migration capacity of CM and IM subpopulations.
CD14(2+)CD16(-)(经典单核细胞[CM])、CD14(2+)CD16(+)(中间单核细胞[IM])和CD14(+)CD16(2+)(非经典单核细胞[NCM])。我们之前表明,肥胖与IM和NCM比例增加有关。我们的目标是解读肥胖相关低度炎症中每个单核细胞亚群的迁移和炎症功能。本研究纳入了26名健康、体重正常且非糖尿病的志愿者(C组)和40名肥胖非糖尿病(Ob组)个体。我们探究了C组和Ob组受试者各亚群中18种炎症基因的基因表达谱,并测量了上调基因的蛋白质表达。然后我们测试了两组中它们对Toll样受体(TLR)信号的功能反应。我们发现Ob组所有单核细胞亚群中CX3CR1表达增加,CM和IM中CCR2和CCR5表达增加。我们发现CCR2和CX3CR1表达与高密度脂蛋白胆固醇呈负相关,而CCR5表达与肥胖相关代谢特征呈正相关。与C组相比,Ob组CM和NCM在细菌脂多糖(LPS)和病毒单链RNA(ssRNA)刺激下炎症蛋白的产生更高。我们的研究突出了肥胖状态下单核细胞炎症表型增强,对TLR4和TLR8刺激反应更高。此外,这表明CM和IM亚群的迁移能力增强。