Granulomatous response to Coxiella burnetii, the agent of Q fever: the lessons from gene expression analysis

Delphine Faugaret (1) , Amira Ben Amara (1) , Julie Alingrin (1) , Aurélie Daumas (1) , Amélie Delaby (1, 2) , Catherine Lépolard (1) , Didier Raoult (1) , Julien Textoris (1, 3) , Jean-Louis Mege (1)

1 URMITE - Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes
2 CIML - Centre d'Immunologie de Marseille - Luminy
3 BIOMERIEUX

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.

Mots clés: granuloma; Q fever; Coxiella burnetii; BCG; transcriptome; type 1 interferon pathway

Domaines: Microbiologie et Parasitologie

Delphine Faugaret, Amira Ben Amara, Julie Alingrin, Aurélie Daumas, Amélie Delaby, et al.. Granulomatous response to Coxiella burnetii, the agent of Q fever: the lessons from gene expression analysis. Frontiers in Cellular and Infection Microbiology, 2014, 4, ⟨10.3389/fcimb.2014.00172⟩. ⟨hal-01771477⟩