title: Intact interferon-γ response against Coxiella burnetii by peripheral blood mononuclear cells in chronic Q fever.
abstract: OBJECTIVE
  Q fever is caused by Coxiella burnetii, an intracellular bacterium that infects phagocytes. The aim of the present study was to investigate whether the C. burnetii-induced IFN-γ response is defective in chronic Q fever patients.
  
  
  METHODS
  IFN-γ was measured in supernatants of C. burnetii-stimulated peripheral blood mononuclear cells (PBMCs) of 17 chronic Q fever patients and 17 healthy individuals. To assess IFN-γ responses, expression profiles of IFN-γ-induced genes in C. burnetii-stimulated PBMCs were studied in six patients and four healthy individuals. Neopterin was measured in PBMC supernatants (of eight patients and four healthy individuals) and in sera (of 21 patients and 11 healthy individuals). In a genetic association study, polymorphisms in genes involved in the Th1-cytokine response were analysed in a cohort of 139 chronic Q fever patients and a cohort of 220 control individuals with previous exposition to C. burnetii.
  
  
  RESULTS
  IFN-γ production by C. burnetii-stimulated PBMCs from chronic Q fever patients was significantly higher than in healthy controls. Many IFN-γ response genes were strongly upregulated in PBMCs of patients. Neopterin levels were significantly higher in PBMC supernatants and sera of patients. The IL12B polymorphisms rs3212227 and rs2853694 were associated with chronic Q fever.
  
  
  CONCLUSIONS
  IFN-γ production, as well as the response to IFN-γ, is intact in chronic Q fever patients, and even higher than in healthy individuals. Polymorphisms in the IL-12p40 gene are associated with chronic Q fever. Thus, a deficiency in IFN-γ responses does not explain the failure to clear the infection. The genetic data suggest, however, that the IL-12/IFN-γ pathway does play a role.
authors.affiliation: Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands. Electronic address: Teske.Schoffelen@radboudumc.nl.
authors.forename: T
authors.initials: T
authors.lastname: Schoffelen
authors.affiliation: URMITE, CNRS UMR 7278, IRD 198, INSERM 1095, Aix-Marseille University, Marseille, France.
authors.forename: J
authors.initials: J
authors.lastname: Textoris
authors.affiliation: Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: C P
authors.initials: CP
authors.lastname: Bleeker-Rovers
authors.affiliation: URMITE, CNRS UMR 7278, IRD 198, INSERM 1095, Aix-Marseille University, Marseille, France.
authors.forename: A
authors.initials: A
authors.lastname: Ben Amara
authors.affiliation: Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: J W M
authors.initials: JW
authors.lastname: van der Meer
authors.affiliation: Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: M G
authors.initials: MG
authors.lastname: Netea
authors.affiliation: URMITE, CNRS UMR 7278, IRD 198, INSERM 1095, Aix-Marseille University, Marseille, France.
authors.forename: J-L
authors.initials: JL
authors.lastname: Mege
authors.affiliation: Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: van Deuren
authors.affiliation: Department of Infectious Diseases, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: van de Vosse
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D016997:Coxiella burnetii / Q000276:immunology*; D005260:Female; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000378:metabolism*; D053762:Interleukin-12 Subunit p40 / Q000235:genetics; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D019798:Neopterin / Q000032:analysis / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D011778:Q Fever / Q000276:immunology*
chemical_list: D053762:Interleukin-12 Subunit p40; D019798:Neopterin; D007371:Interferon-gamma
keywords: Chronic Q fever; Coxiella burnetii; Disease susceptibility; Gene expression profiling; Genetic variation; Interferon-γ; Interleukin-12; Neopterin; Q fever; Single nucleotide polymorphism