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

Melenotte, Cléa; Mezouar, Soraya; Amara, Amira Ben; Benatti, S. V.; Chiaroni, Jacques; Devaux, Christian; Costello, Régis; Kroemer, Guido; Mège, Jean‐Louis; Raoult, Didier

doi:10.1371/journal.pone.0217542

Cited by 14 publications

(17 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Over the past 3 years, we have reported results suggesting that the bacterium Coxiella burnetii , responsible of Q fever, was associated with a higher frequency of Non-Hodgkin Lymphoma (NHL) in C. burnetii -infected patients compared to the general population (Melenotte et al, 2016). Recently, we investigated the transcriptional signature that could be associated with the development of NHL in Q fever patients and found an over-expression of genes involved in anti-apoptotic process and a repression of pro-apoptotic genes (Melenotte et al, 2019). Since cell surface expression of E-cad and release of sE-cad have been associated to various pathogenic bacteria known for inducing solid tumors, we have also investigated the levels of expression of these molecules in Q fever patients and observed a significant release of sE-cad in their sera and a down-regulation of E-cad mRNA expression.…”

Section: Release Of Soluble E-cadherin After Bacterial Infection As Amentioning

confidence: 99%

The E-Cadherin Cleavage Associated to Pathogenic Bacteria Infections Can Favor Bacterial Invasion and Transmigration, Dysregulation of the Immune Response and Cancer Induction in Humans

2019

Self Cite

View full text Add to dashboard Cite

Once bound to the epithelium, pathogenic bacteria have to cross epithelial barriers to invade their human host. In order to achieve this goal, they have to destroy the adherens junctions insured by cell adhesion molecules (CAM), such as E-cadherin (E-cad). The invasive bacteria use more or less sophisticated mechanisms aimed to deregulate CAM genes expression or to modulate the cell-surface expression of CAM proteins, which are otherwise rigorously regulated by a molecular crosstalk essential for homeostasis. Apart from the repression of CAM genes, a drastic decrease in adhesion molecules on human epithelial cells can be obtained by induction of eukaryotic endoproteases named sheddases or through synthesis of their own (prokaryotic) sheddases. Cleavage of CAM by sheddases results in the release of soluble forms of CAM. The overexpression of soluble CAM in body fluids can trigger inflammation and pro-carcinogenic programming leading to tumor induction and metastasis. In addition, the reduction of the surface expression of E-cad on epithelia could be accompanied by an alteration of the anti-bacterial and anti-tumoral immune responses. This immune response dysfunction is likely to occur through the deregulation of immune cells homing, which is controlled at the level of E-cad interaction by surface molecules αE integrin (CD103) and lectin receptor KLRG1. In this review, we highlight the central role of CAM cell-surface expression during pathogenic microbial invasion, with a particular focus on bacterial-induced cleavage of E-cad. We revisit herein the rapidly growing body of evidence indicating that high levels of soluble E-cad (sE-cad) in patients’ sera could serve as biomarker of bacterial-induced diseases.

show abstract

Section: Release Of Soluble E-cadherin After Bacterial Infection As Amentioning

confidence: 99%

The E-Cadherin Cleavage Associated to Pathogenic Bacteria Infections Can Favor Bacterial Invasion and Transmigration, Dysregulation of the Immune Response and Cancer Induction in Humans

2019

Self Cite

View full text Add to dashboard Cite

show abstract

“…The Rituximab used in the treatment of NHL patients may overcome BCL-2-mediated chemoresistance through the inhibition of IL-10, thus down-regulating BCL-2 expression (Park et al, 2009). By investigating a specific gene signature for Q fever patients by microarray, we recently found that specific genes involved in anti-apoptotic process were over-expressed compared to samples from healthy donors, and that pro-apoptotic genes were repressed (Melenotte et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…Thereby, we investigated the transcriptional signature associated with the development of NHL using the PBMCs of patients with Q fever. By analyzing their gene expression by microarray, we found the over-expression of genes involved in anti-apoptotic process and repression of pro-apoptotic genes as compared to samples from healthy donors (Melenotte et al, 2019). Yet, the early molecular events controlling the balance between remission and progression toward more severe diseases remain elusive.…”

Section: Introductionmentioning

confidence: 99%

High Concentrations of Serum Soluble E-Cadherin in Patients With Q Fever

Mezouar

Osman

Melenotte

et al. 2019

Front. Cell. Infect. Microbiol.

Self Cite

View full text Add to dashboard Cite

Cadherins switching is a hallmark of neoplasic processes. The E-cadherin (E-cad) subtype is one of the surface molecules regulating cell-to-cell adhesion. After its cleavage by sheddases, a soluble fragment (sE-cad) is released that has been identified as a pro-carcinogenic inflammatory signal in several bacteria-induced cancers. Recently we reported that Q fever, a disease due to Coxiella burnetii infection, can be complicated by occurrence of non-Hodgkin lymphoma (NHL). Therefore, we studied E-cad switching in Q fever. The sE-cad levels were found increased in the sera of acute and persistent Q fever patients, whereas they remained at the baseline in controls groups of healthy donors, people cured of Q fever, patients suffering from unrelated inflammatory diseases, and past Q fever patients who developed NHL. These results indicate that sE-cad can be considered as a new biomarker of C. burnetii infection rather than a marker of NHL-associated to Q fever. We wondered if changes in sE-cad reflected variations in the CDH1 gene transcription. The expression of E-cad mRNA and its intracellular ligand β-catenin was down-regulated in peripheral blood mononuclear cells (PBMCs) of patients with either acute or persistent forms of Q fever. Indeed, a lower cell-surface expression of E-cad was measured in a minority (<5%) subpopulation of HLADR + /CD16 + monocytes from patients with acute Q fever. However, a very strong increase in E-cad expression was observed on more than 30% of the HLADR + /CD16 + monocytes of persistent Q fever patients, a cell subpopulation known to be a target for C. burnetii in humans. An experimental in vitro infection of healthy donors' PBMCs with C. burnetii , was performed to directly evaluate the link between C. burnetii interaction with PBMCs and their E-cad expression. A significant increase in the percentage of HLADR + /CD16 + monocytes expressing E-cad was measured after PBMCs had been incubated for 8 h with C. burnetii Nine Mile strain. Altogether, these data demonstrate that C. burnetii severely impairs the E-cad expression in circulating cells of Q fever patients.

show abstract

“…In another study conducted by Melanotte et al, it was demonstrated that patients with C . burnetii lymphadenitis presented significantly elevated levels of BCL2 and ETS1 mRNAs, which may indicate the upregulation of anti-apoptotic processes and the fact that lymphadenitis might constitute a critical step towards lymphomagenesis [ 121 ]. The association of Q fever with NHL requires further study.…”

Section: Coxiella Burnetii ( C Burnetii ) and Various Nhlmentioning

confidence: 99%

Bacterial Infection and Non-Hodgkin B-Cell Lymphoma: Interactions between Pathogen, Host and the Tumor Environment

Biernat

Wróbel

2021

IJMS

View full text Add to dashboard Cite

Non-Hodgkin B-cell lymphomas (NHL) are a heterogeneous group of lymphoid neoplasms with complex etiopathology, rich symptomatology, and a variety of clinical courses, therefore requiring different therapeutic approaches. The hypothesis that an infectious agent may initiate chronic inflammation and facilitate B lymphocyte transformation and lymphogenesis has been raised in recent years. Viruses, like EBV, HTLV-1, HIV, HCV and parasites, like Plasmodium falciparum, have been linked to the development of lymphomas. The association of chronic Helicobacter pylori (H. pylori) infection with mucosa-associated lymphoid tissue (MALT) lymphoma, Borrelia burgdorferi with cutaneous MALT lymphoma and Chlamydophila psittaci with ocular adnexal MALT lymphoma is well documented. Recent studies have indicated that other infectious agents may also be relevant in B-cell lymphogenesis such as Coxiella burnettii, Campylobacter jejuni, Achromobacter xylosoxidans, and Escherichia coli. The aim of the present review is to provide a summary of the current literature on infectious bacterial agents associated with B-cell NHL and to discuss its role in lymphogenesis, taking into account the interaction between infectious agents, host factors, and the tumor environment.

show abstract

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

Cited by 14 publications

References 33 publications

The E-Cadherin Cleavage Associated to Pathogenic Bacteria Infections Can Favor Bacterial Invasion and Transmigration, Dysregulation of the Immune Response and Cancer Induction in Humans

The E-Cadherin Cleavage Associated to Pathogenic Bacteria Infections Can Favor Bacterial Invasion and Transmigration, Dysregulation of the Immune Response and Cancer Induction in Humans

High Concentrations of Serum Soluble E-Cadherin in Patients With Q Fever

Bacterial Infection and Non-Hodgkin B-Cell Lymphoma: Interactions between Pathogen, Host and the Tumor Environment

Contact Info

Product

Resources

About