title: Imbalance of circulating monocyte subsets and PD-1 dysregulation in Q fever endocarditis: the role of IL-10 in PD-1 modulation.
abstract: Q fever endocarditis, a severe complication of Q fever, is associated with a defective immune response, the mechanisms of which are poorly understood. We hypothesized that Q fever immune deficiency is related to altered distribution and activation of circulating monocyte subsets. Monocyte subsets were analyzed by flow cytometry in peripheral blood mononuclear cells from patients with Q fever endocarditis and controls. The proportion of classical monocytes (CD14(+)CD16(-) monocytes) was similar in patients and controls. In contrast, the patients with Q fever endocarditis exhibited a decrease in the non-classical and intermediate subsets of monocytes (CD16(+) monocytes). The altered distribution of monocyte subsets in Q fever endocarditis was associated with changes in their activation profile. Indeed, the expression of HLA-DR, a canonical activation molecule, and PD-1, a co-inhibitory molecule, was increased in intermediate monocytes. This profile was not restricted to CD16(+) monocytes because CD4(+) T cells also overexpressed PD-1. The mechanism leading to the overexpression of PD-1 did not require the LPS from C. burnetii but involved interleukin-10, an immunosuppressive cytokine. Indeed, the incubation of control monocytes with interleukin-10 led to a higher expression of PD-1 and neutralizing interleukin-10 prevented C. burnetii-stimulated PD-1 expression. Taken together, these results show that the immune suppression of Q fever endocarditis involves a cross-talk between monocytes and CD4(+) T cells expressing PD-1. The expression of PD-1 may be useful to assess chronic immune alterations in Q fever endocarditis.
authors.affiliation: Aix Marseille Université, Unité de Recherche sur les Maladies Infectieuses Tropicales et Emergentes, UMR 63, CNRS 7278, IRD 198, INSERM U1095, Marseille, France; Inserm UMR 1068, Centre de Recherche en Cancérologie de Marseille, Marseille, France.
authors.forename: Mignane B
authors.initials: MB
authors.lastname: Ka
authors.affiliation: Inserm UMR 1068, Centre de Recherche en Cancérologie de Marseille, Marseille, France.
authors.forename: Françoise
authors.initials: F
authors.lastname: Gondois-Rey
authors.affiliation: Aix Marseille Université, Unité de Recherche sur les Maladies Infectieuses Tropicales et Emergentes, UMR 63, CNRS 7278, IRD 198, INSERM U1095, Marseille, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Capo
authors.affiliation: Aix Marseille Université, Unité de Recherche sur les Maladies Infectieuses Tropicales et Emergentes, UMR 63, CNRS 7278, IRD 198, INSERM U1095, Marseille, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Textoris
authors.affiliation: Aix Marseille Université, Unité de Recherche sur les Maladies Infectieuses Tropicales et Emergentes, UMR 63, CNRS 7278, IRD 198, INSERM U1095, Marseille, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Million
authors.affiliation: Aix Marseille Université, Unité de Recherche sur les Maladies Infectieuses Tropicales et Emergentes, UMR 63, CNRS 7278, IRD 198, INSERM U1095, Marseille, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Raoult
authors.affiliation: Inserm UMR 1068, Centre de Recherche en Cancérologie de Marseille, Marseille, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Olive
authors.affiliation: Aix Marseille Université, Unité de Recherche sur les Maladies Infectieuses Tropicales et Emergentes, UMR 63, CNRS 7278, IRD 198, INSERM U1095, Marseille, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mege
mesh_terms: D000328:Adult; D000368:Aged; D016997:Coxiella burnetii / Q000276:immunology; D004697:Endocarditis, Bacterial / Q000276:immunology* / Q000382:microbiology; D005260:Female; D015870:Gene Expression; D006684:HLA-DR Antigens / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology*; D061026:Programmed Cell Death 1 Receptor / Q000097:blood*; D011778:Q Fever / Q000276:immunology* / Q000382:microbiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
chemical_list: D006684:HLA-DR Antigens; C508609:IL10 protein, human; C105992:PDCD1 protein, human; D061026:Programmed Cell Death 1 Receptor; D016753:Interleukin-10