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

Soraya Mezouar,Camélia Slimani,Christian A Devaux,Jean-Louis Mege,Ikram Omar Osman,Céline Chartier,Didier Raoult,Cléa Melenotte

doi:10.3389/fcimb.2019.00219

Abstract

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.

Highlights

Q fever is a zoonosis most of the time transmitted to humans by animal products contaminated with Coxiella burnetii, a strict intracellular Gram-negative bacterium (Maurin and Raoult, 1999)
S-E-cad release was significantly increased in patients with acute Q fever (n = 10; p = 0.0034) and persistent Q fever (n = 6; p = 0.0014) compared to the two control groups, the healthy donors’ group (n = 13), the people cured of Q fever (n = 10), and the group of patients suffering from rheumatoid arthritis (n = 8). These results indicated that soluble form of E-cad (sE-cad) cleavage and release were observed in the two forms of Q fever and achieved independently of any inflammatory reaction
Despite the significant global decrease in E-cad mRNA observed with the peripheral blood mononuclear cells (PBMCs) of both acute and persistent Q fever patients, we found a surprising over-expression of cell-surface E-cad protein on the HLADR+/CD16+ cells of persistent Q fever patients

Summary

Introduction

Q fever is a zoonosis most of the time transmitted to humans by animal products contaminated with Coxiella burnetii, a strict intracellular Gram-negative bacterium (Maurin and Raoult, 1999). The bacteria usually infect human by the aerosol route and Q fever usually occurs 2–6 weeks after exposure (van Schaik et al, 2013). Symptomatic infections (10–60% of cases), usually resolve spontaneously in a few weeks. This clinical form of the disease, called acute Q fever, is characterized by high fever, headache, myalgia, pneumonia, and hepatitis (Eldin et al, 2017). In less than 5% of cases, the symptoms do not resolve and settle in a persistent way (Melenotte et al, 2018). Other disorders were described in association with persistent focalized C. burnetii infections, including interstitial lung diseases, persistent granulomatous hepatitis, and B-cell lymphoma (Ramos et al, 2012; Melenotte et al, 2016, 2018)

Objectives

Methods

Results

Conclusion