AUTHOR=Faugaret Delphine , Ben Amara Amira , Alingrin Julie , Daumas Aurélie , Delaby Amélie , Lépolard Catherine , Raoult Didier , Textoris Julien , Mège Jean-Louis 

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

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=4

YEAR=2014

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2014.00172

DOI=10.3389/fcimb.2014.00172

ISSN=2235-2988

ABSTRACT=<p>The formation of granulomas is associated with the resolution of Q fever, a zoonosis due to <italic>Coxiella burnetii</italic>; however the molecular mechanisms of granuloma formation remain poorly understood. We generated human granulomas with peripheral blood mononuclear cells (PBMCs) and beads coated with <italic>C. burnetii</italic>, 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 <italic>C. burnetii</italic> 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. <italic>C. burnetii</italic> 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 <italic>C. burnetii</italic> is characterized by the activation of type 1 interferon pathway.</p>