title: Granulomatous response to Coxiella burnetii, the agent of Q fever: the lessons from gene expression analysis.
abstract: The formation of granulomas is associated with the resolution of Q fever, a zoonosis due to Coxiella burnetii; however the molecular mechanisms of granuloma formation remain poorly understood. We generated human granulomas with peripheral blood mononuclear cells (PBMCs) and beads coated with C. burnetii, using BCG extracts as controls. A microarray analysis showed dramatic changes in gene expression in granuloma cells of which more than 50% were commonly modulated genes in response to C. burnetii and BCG. They included M1-related genes and genes related to chemotaxis. The inhibition of the chemokines, CCL2 and CCL5, directly interfered with granuloma formation. C. burnetii granulomas also expressed a specific transcriptional profile that was essentially enriched in genes associated with type I interferon response. Our results showed that granuloma formation is associated with a core of transcriptional response based on inflammatory genes. The specific granulomatous response to C. burnetii is characterized by the activation of type 1 interferon pathway.
authors.affiliation: Aix Marseille Université, URMITE, UMR CNRS 7278, IRD 198, INSERM 1095 Marseille, France ; AltraBio SAS Lyon, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Faugaret
authors.affiliation: Aix Marseille Université, URMITE, UMR CNRS 7278, IRD 198, INSERM 1095 Marseille, France.
authors.forename: Amira
authors.initials: A
authors.lastname: Ben Amara
authors.affiliation: Aix Marseille Université, URMITE, UMR CNRS 7278, IRD 198, INSERM 1095 Marseille, France.
authors.forename: Julie
authors.initials: J
authors.lastname: Alingrin
authors.affiliation: Aix Marseille Université, URMITE, UMR CNRS 7278, IRD 198, INSERM 1095 Marseille, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Daumas
authors.affiliation: Aix Marseille Université, URMITE, UMR CNRS 7278, IRD 198, INSERM 1095 Marseille, France ; Centre d'Immunologie de Marseille-Luminy, Parc Scientifique et Technologique Marseille, France.
authors.forename: Amélie
authors.initials: A
authors.lastname: Delaby
authors.affiliation: Aix Marseille Université, URMITE, UMR CNRS 7278, IRD 198, INSERM 1095 Marseille, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Lépolard
authors.affiliation: Aix Marseille Université, URMITE, UMR CNRS 7278, IRD 198, INSERM 1095 Marseille, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Raoult
authors.affiliation: Aix Marseille Université, URMITE, UMR CNRS 7278, IRD 198, INSERM 1095 Marseille, France ; Unité Mixte BioMérieux-HCL, Hôpital Edouard Herriot - Pav P Lyon, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Textoris
authors.affiliation: Aix Marseille Université, URMITE, UMR CNRS 7278, IRD 198, INSERM 1095 Marseille, France.
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mège
mesh_terms: D000328:Adult; D000368:Aged; D016997:Coxiella burnetii / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling; D006099:Granuloma / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000382:microbiology; D008297:Male; D008875:Middle Aged; D011778:Q Fever / Q000235:genetics* / Q000378:metabolism / Q000382:microbiology*
keywords: BCG; Coxiella burnetii; Q fever; granuloma; transcriptome; type 1 interferon pathway