Date Published: June 10, 2019
Publisher: Public Library of Science
Author(s): Cléa Melenotte, Soraya Mezouar, Amira Ben Amara, Simon Benatti, Jacques Chiaroni, Christian Devaux, Régis Costello, Guido Kroemer, Jean-Louis Mege, Didier Raoult, Riccardo Dolcetti.
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.
NHL is the most common type (~90%) of lymphoma in humans. Many risk factors have been identified for malignant transformation: immune disorders, infection, lifestyle, genetics, family history and profession . The most common type of lymphoma is diffuse large B-cell lymphoma (DLBCL) which manifests as fast-growing nodal or extranodal tumors . Neoplasic transformation from germinal center B cells results from the accumulation of genetic modifications. Some indolent follicular lymphomas (FL) can evolve into more aggressive cancers, such as DLBCL or Burkitt lymphoma (BL) . Gene expression profiling using microrrays or RNAseq has revealed the huge diversity of mechanisms accounting for neoplasic transformation . This technology has identified two molecularly distinct forms of DLBCL, one characteristic of germinal center B-cells (GCB) and one of activated-B cells (ABC) .
The present study identifies a specific transcriptomic signature of Cb-NHL among patients with persistent C. burnetii infection strengthening the link between Q fever and the development of NHL.