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Granulomatous response to Coxiella burnetii, the agent of Q fever: Activation of type I interferon-related genes

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 and beads coated with C. burnetii, using BCG extracts as controls. A microarray analysis showed dramatic changes in gene expression in granuloma cells compared with peripheral blood mononuclear cells. About 60% of modulated genes were common to C. burnetii and BCG granulomas including M1-related genes. C. burnetii granulomas also expressed a specific transcriptional profile that was essentially enriched in genes associated with type I interferon response (IFI44, IFI44L, IFI6, OAS1, OAS2, OAS3, ISG15, IFIT1, IFITM2, IFITM3, MX1 and MX2). Real-time RT-PCR confirmed that C. burnetii especially increased the expression of interferon-stimulated genes in granulomas generated from controls or Q fever patients. Our results showed that granuloma formation is associated with a core of transcriptional response, but that the granulomatous response to C. burnetii is characterized by the activation of type I interferon-related genes, conferring a new role for type I interferon response in the control of C. burnetii infection. Human Peripheral Blood Mononuclear Cells (PBMC) were co-cultured with beads coated with Mycobacterium bovis strain Bacille Calmette Guerin (BCG) extracts or Coxiella burnetii (C.burnetii) extracts for 8 days and PBMC at day 0 were used as controls. For each condition ( unstimulated, BCG and C.burnetii), each microarray is a replicate of the same biological sample.

ORGANISM(S): Homo sapiens

SUBMITTER: Julien Textoris

PROVIDER: E-GEOD-37666 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Granulomatous response to Coxiella burnetii, the agent of Q fever: Activation of type I interferon-related genes

Project description: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 and beads coated with C. burnetii, using BCG extracts as controls. A microarray analysis showed dramatic changes in gene expression in granuloma cells compared with peripheral blood mononuclear cells. About 60% of modulated genes were common to C. burnetii and BCG granulomas including M1-related genes. C. burnetii granulomas also expressed a specific transcriptional profile that was essentially enriched in genes associated with type I interferon response (IFI44, IFI44L, IFI6, OAS1, OAS2, OAS3, ISG15, IFIT1, IFITM2, IFITM3, MX1 and MX2). Real-time RT-PCR confirmed that C. burnetii especially increased the expression of interferon-stimulated genes in granulomas generated from controls or Q fever patients. Our results showed that granuloma formation is associated with a core of transcriptional response, but that the granulomatous response to C. burnetii is characterized by the activation of type I interferon-related genes, conferring a new role for type I interferon response in the control of C. burnetii infection.

2015-05-01 | GSE37666 | GEO

Human peripheral blood mononuclear cells stimulated in vitro by BCG strains or PPD

Project description:This experiment explored the transcriptional response of human peripheral blood mononuclear cells (PBMC) isolated from BCG-vaccinated individuals following 6 days of in vitro stimulation with 2x10^5 cfu of different Bacillus Calmette-Guérin (BCG) strains or 100 ng/ml Mycobacterium tuberculosis-derived purified protein derivative (PPD). The BCG strains used were BCG Russia (Russian BCG-I sub-strain), BCG Japan (Tokyo 172 sub-strain), BCG Denmark (Danish 1331 sub-strain) & BCG Pasteur.

2022-01-26 | E-MTAB-11345 | biostudies-arrayexpress

Early response of Coxiella burnetii to temperature stress

Project description:Transcriptional profiling of Coxiella burnetii phase I (RSA 493) submitting either to Cold and Heat shock comparing to control untreated Coxiella burnetii phase I (RSA 493) grown at 35Â°C. Four experiments : Cold shock 30 min Vs 35Â°C; Cold shock 60 min Vs 35Â°C; Heat shock 30 min Vs 35Â°C; Heat shock 60 min Vs 35Â°C 3 biological replicates, independently grown and harvested. Four replicate per array.

2011-01-01 | E-GEOD-21778 | biostudies-arrayexpress

Coxiella burnetii, the agent of Q fever, persists in adipocytes

Project description:Coxiella burnetii, the agent of Q fever, persists in humans despite specific immune responses: however, its reservoir remains unknown. We detected C. burnetii in adipose tissue from BALB/c and C57/BL6 mice 4 months after infection when no bacteria were found in other tissues. C. burnetii infected cultivated adipocytes, replicated within late phagosomes and induced a transcriptional program that was enriched for the expression of genes associated with inflammatory response, hormonal responses and cytoskeleton. 3T3-L1 (ATCC) differentiated adipocytes were stimulated or not with Coxiella burnetii (NMI) at a ratio of 50 bacteria per cell. Four biological replicates were analyzed in each group. Due to technical reason, one unstimulated sample was discarded from the analysis.

2014-05-25 | E-GEOD-46335 | biostudies-arrayexpress

Genome-wide characterization of a novel necrotic granuloma model of latent tuberculosis infection and reactivation in mice

Project description:We sought to develop and characterize a novel paucibacillary model in mice, which develop necrotic lung granulomas following infection with Mycobacterium tuberculosis. Paucibacillary infection was established, recapitulating the sterilizing activities of human LTBI regimens. TNF neutralization led to increased lung bacillary load, disrupted granuloma architecture with expanded necrotic foci and reduced tissue hypoxia, and accelerated animal mortality. TNF-neutralized mouse lungs and sera showed significant upregulation of IFN?, IL-1?, IL-6, IL-10, CCL2, CCL3, and matrix metalloproteinase genes Six weeks after aerosol-immunization with recombinant M. bovis BCG overexpressing the 30-kilodalton antigen, C3HeB/FeJ mice were aerosol-infected with M. tuberculosis H37Rv. Six weeks later, mice were treated with one of three standard regimens for latent TB infection (LTBI) or TNF-neutralizing antibody. Mouse lungs were analyzed by histology, positron emission tomography/computed tomography, whole-genome microarrays, and RT-PCR. Lungs and sera were studied by multiplex enzyme-linked immunosorbent assays

2014-02-20 | E-GEOD-55183 | biostudies-arrayexpress

Genotyping of Coxiella burnetii strains collection

Project description:Genotyping based on genomic comparative hybridization of different isolates of coxiella burnetii compared to NMI reference strain Two-condition experiment, NMI vs. isolates. One replicate per isolate.

2011-12-31 | E-GEOD-31543 | biostudies-arrayexpress

Interferon-Î³ response against C. burnetii of peripheral blood mononuclear cells in the development of chronic Q fever

Project description:Background: Q fever is caused by the Coxiella burnetii, an intracellular bacterium that infects mononuclear cells. In some individuals, it causes a persistent cardiovascular infection (chronic Q fever). The aim of present study was to investigate the C. burnetii-induced IFN-Î³ response in chronic Q fever patients. Methods: IFN-Î³ was measured in supernatants of C. burnetii-stimulated peripheral blood mononuclear cells (PBMCs) of patients. Gene-expression profiles of the IFN-Î³ pathway in PBMCs after incubation with C. burnetii were compared between chronic Q fever patients and control individuals. Results: IFN-Î³ production by PBMCs of chronic Q fever patients incubated with C. burnetii in vitro, was significantly higher compared to controls. In transcriptome analysis, genes downstream of IFN-Î³ were strongly upregulated in patients. Conclusion: Present study showed that IFN-Î³ production and the response to IFN-Î³ seems to be intact in chronic Q fever patients. PBMC were purified from Q fever patients (n=6) or healthy volunteers (n=4), and then stimulated by Coxiella burnetii, LPS or left untreated (NS)

2016-03-13 | E-GEOD-66476 | biostudies-arrayexpress

Early response of Coxiella burnetii to temperature stress

2011-01-01 | GSE21778 | GEO

Interferon-γ response against C. burnetii of peripheral blood mononuclear cells in the development of chronic Q fever

Project description:Background: Q fever is caused by the Coxiella burnetii, an intracellular bacterium that infects mononuclear cells. In some individuals, it causes a persistent cardiovascular infection (chronic Q fever). The aim of present study was to investigate the C. burnetii-induced IFN-γ response in chronic Q fever patients. Methods: IFN-γ was measured in supernatants of C. burnetii-stimulated peripheral blood mononuclear cells (PBMCs) of patients. Gene-expression profiles of the IFN-γ pathway in PBMCs after incubation with C. burnetii were compared between chronic Q fever patients and control individuals. Results: IFN-γ production by PBMCs of chronic Q fever patients incubated with C. burnetii in vitro, was significantly higher compared to controls. In transcriptome analysis, genes downstream of IFN-γ were strongly upregulated in patients. Conclusion: Present study showed that IFN-γ production and the response to IFN-γ seems to be intact in chronic Q fever patients.

2016-03-13 | GSE66476 | GEO

Genotyping of Coxiella burnetii strains collection

Project description:Genotyping based on genomic comparative hybridization of different isolates of coxiella burnetii compared to NMI reference strain

2011-12-31 | GSE31543 | GEO

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