A transcriptional signature associated with non-Hodgkin lymphoma in the blood of patients with Q fever

Cléa Melenotte; Soraya Mezouar; Amira Ben Amara; Simon Benatti; Jacques Chiaroni; Christian Devaux; Régis Costello; Guido Kroemer; Jean-Louis Mege; Didier Raoult

doi:10.1371/journal.pone.0217542

A transcriptional signature associated with non-Hodgkin lymphoma in the blood of patients with Q fever

PLoS One. 2019 Jun 10;14(6):e0217542. doi: 10.1371/journal.pone.0217542. eCollection 2019.

Authors

Cléa Melenotte¹, Soraya Mezouar¹, Amira Ben Amara¹, Simon Benatti², Jacques Chiaroni^{3

4}, Christian Devaux¹, Régis Costello⁵, Guido Kroemer^{6

7

8

9

10

11

12

13}, Jean-Louis Mege¹, Didier Raoult¹

Affiliations

¹ Aix-Marseille Univ, IRD, APHM, MEPHI, IHU-Méditerranée Infection, Marseille, France.
² Infectious Diseases, ASST Papa Giovanni XXIII, Bergamo, Italy.
³ Établissement Français du Sang Alpes Méditerranée, Marseille, France.
⁴ Aix-Marseille University, CNRS, ADES, "Biologie des Groupes Sanguins", Marseille, France.
⁵ Service d'hématologie de la Conception, Assistance publique des hôpitaux de Marseille, Marseille, France.
⁶ Gustave Roussy Cancer Campus, Villejuif, France.
⁷ INSERM, U1138, Paris, France.
⁸ Equipe 11 labellisée par la Ligue Nationale contre le Cancer, Centre de Recherche des Cordeliers, Paris, France.
⁹ Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
¹⁰ Metabolomics and Cell Biology Platforms, Gustave Roussy Cancer Campus, Villejuif, France.
¹¹ Université Pierre et Marie Curie, Paris, France.
¹² Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France.
¹³ Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden.

Abstract

Coxiella burnetii, the agent causing Q fever, has been associated with B-cell non-Hodgkin lymphoma (NHL). To better clarify this link, we analysed the genetic transcriptomic profile of peripheral blood leukocytes from patients with C. burnetii infection to identify possible links to lymphoma. Microarray analyses revealed that 1189 genes were expressed differently (p <.001 and fold change ≥4) in whole blood of patients with C. burnetii infection compared to controls. In addition, 95 genes expressed in patients with non-Hodgkin lymphoma (NHL) and in patients with C. burnetii persistent infection have allowed us to establish the 'C. burnetii-associated NHL signature'. Among these, 33 genes previously found modulated in C. burnetii-associated -NHL by the microarray analysis were selected and their mRNA expression levels were measured in distinct C. burnetii-induced pathologies, namely, acute Q fever, focalized persistent infection, lymphadenitis and C.burnetii-associated NHL. Specific genes involved in anti-apoptotic process were found highly expressed in leukocytes from patients with C. burnetii associated-NHL: MIR17HG, REL and SP100. This signature differed from that found for NHL-control group. Patients with C. burnetii lymphadenitis presented significant elevated levels of BCL2 and ETS1 mRNAs. Altogether, we identified a specific transcriptionnal signature for NHL during C. burnetii infection reflecting the up-regulation of anti-apoptotic processes and the fact that lymphadenitis might constitute a critical step towards lymphomagenesis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis / genetics
Coxiella burnetii / pathogenicity
Female
Gene Expression Profiling / methods
Humans
Leukocytes, Mononuclear / metabolism
Leukocytes, Mononuclear / microbiology
Lymphadenitis / genetics
Lymphadenitis / microbiology
Lymphoma, Non-Hodgkin / genetics*
Lymphoma, Non-Hodgkin / metabolism
Lymphoma, Non-Hodgkin / microbiology
Male
Microarray Analysis
Middle Aged
Q Fever / genetics*
Q Fever / microbiology
Transcription, Genetic / genetics*
Up-Regulation / genetics

Grants and funding

Soraya Mezouar was supported by a“Fondation pour la Recherche Médicale” (FRM) postdoctoral fellowship (SPF20151234951). This work was supported by the French Government under the « Investissements d’avenir » (Investments for the Future) program managed by the Agence Nationale de la Recherche (ANR, fr: National Agency for Research), (reference: Méditerranée Infection 10-IAHU-03). -This work was also supported by Région Provence Alpes Côte d’Azur and European funding FEDER PRIMMI (Fonds Européen de Développement Régional - Plateformes de Recherche et d’Innovation Mutualisées Méditerranée Infection) -GK is supported by -GK is supported by the Ligue contre le Cancer Comité de Charente-Maritime (équipe labellisée); AgenceNational de la Recherche (ANR) – Projets blancs; ANR under the frame of E-Rare-2, the ERA-Net for Research on Rare Diseases; Association pour la recherche sur le cancer (ARC); Cancéropôle Ile-de-France; Chancelerie des universités de Paris (Legs Poix), Fondation pour la Recherche Médicale (FRM); a donation by Elior; the European Commission (ArtForce); European Research Area Network on Cardiovascular Diseases (ERA-CVD, MINOTAUR); the European Research Council (ERC); Fondation Carrefour; Institut National du Cancer (INCa); Inserm (HTE); Institut Universitaire de France; LeDucq Foundation; the LabEx Immuno-Oncology; the RHU Torino Lumière; the Seerave Foundation; the SIRIC Stratified Oncology Cell DNA Repair and Tumor Immune Elimination (SOCRATE); the SIRIC Cancer Research and Personalized Medicine (CARPEM); and the Paris Alliance of Cancer Research Institutes (PACRI).