Profiling of the three circulating monocyte subpopulations in human obesity.

Estelle F Devêvre, Mariana Renovato-Martins, Karine Clément, Catherine Sautès-Fridman, Isabelle Cremer, Christine Poitou

Journal: Journal of immunology (Baltimore, Md. : 1950) 2015;194(8):3917-23

PMID: 25786686

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Abstract

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.

Address: 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;; 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; Institute of Cardiometabolism and Nutrition, F-75013 Paris, France; Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière Hospital, Département Nutrition, F-75013 Paris, France; and Centre de Recherche en Nutrition Humaine-Ile de France, F-75013 Paris, France.; INSERM, Unité Mixte de Recherche 1138, Team 13, Centre de Recherches des Cordeliers, F-75006 Paris, France; Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, F-75013 Paris, France; Université Paris Descartes, F-75006 Paris, France;; INSERM, Unité Mixte de Recherche 1138, Team 13, Centre de Recherches des Cordeliers, F-75006 Paris, France; Sorbonne Universités, Université Pierre et Marie Curie-Paris 6, F-75013 Paris, France; Université Paris Descartes, F-75006 Paris, France; [email protected].

DOI: 10.4049/jimmunol.1402655

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MeSH Terms: Adult, CX3C Chemokine Receptor 1, Female, GPI-Linked Proteins, Gene Expression Profiling, Gene Expression Regulation, Humans, Inflammation Mediators, Lipopolysaccharide Receptors, Lipopolysaccharides, Male, Monocytes, Obesity, Receptors, CCR2, Receptors, CCR5, Receptors, Chemokine, Receptors, IgG, Toll-Like Receptor 4, Toll-Like Receptor 8