Biology subjects

Bruneval, P.

Publications and source records attributed to Bruneval, P..

3 recordsLinked to original sources

bioRxiv2024

A macrophage-smooth muscle cell axis influences vascular remodeling through activation of the EGFR pathway in giant cell arteritis

Background.The role of macrophages and vascular resident cells appears to be predominant in the pathophysiology of giant cell arteritis (GCA). We investigated the role of epithelial growth factor receptor (EGFR) signaling pathway, especially through its activation by heparin-binding epidermal growth factor (HB-EGF) and/or amphiregulin (AREG) in this setting. Materials and Methods.Serum samples and temporal artery biopsies (TAB) were obtained from patients enrolled in a prospective cohort of systemic vasculitis. Human THP-1, a monocytic cell line, and human aortic vascular smooth muscle cells (VSMC) were used for in vitro studies. Results.Using multiplex immunohistochemistry, TAB from GCA patients showed higher expression of AREG, HB-EGF, EGFR and phospho-EGFR as compared to control arteries. AREG, HB-EGF and EGFR were predominantly expressed by macrophages, whereas EGFR and phosphor-EGFR were expressed by SMA-positive cells in the media. Increased levels of AREG and HB-EGF were found in culture supernatants of M1 macrophages, whereas M2 macrophages produced only HB-EFG. AREG and HB-EGF did not increase the production of pro-inflammatory cytokines by THP-1 or macrophages but activated the p38 MAPK pathway. Using transcriptomic and Western blot analysis of human aortic VSMC, AREG and especially HB-EGF induced cell proliferation pathway, enhanced interferon alpha and gamma responses, and activation of the MAPK pathway. Finally, AREG and HB-EGF increased both VSMC proliferation and migration, which were completely inhibited by AG1478, an EGFR inhibitor. Conclusion.We show that both AREG and HB-EGF may play a role in the pathophysiology of GCA, especially in the remodeling phase of the disease.

immunology↗

bioRxiv2021

Colonization of dermal arterioles by Neisseria meningitidis provides a safe haven from neutrophils

Neisseria meningitidis, a human-specific bacterium, is responsible for meningitis and fatal fulminant systemic disease. Bacteria colonize blood vessels, rapidly causing devastating vascular damage despite a neutrophil-rich inflammatory infiltrate. How this pathogen escapes the neutrophil response is unknown. Using a humanized mouse model, we show that vascular colonization leads to the recruitment of neutrophils, partially reducing bacterial burden and vascular damage. This partial effect is due to the ability of bacteria to indiscriminately colonize capillaries, venules and arterioles, as observed in human samples. In venules, potent neutrophil recruitment allows efficient bacterial phagocytosis. In contrast, in infected capillaries and arterioles adhesion molecules such as E-Selectin are not expressed on the endothelium and intravascular neutrophil recruitment is minimal. These results show that colonization of capillaries and arterioles by N. meningitidis create an intravascular niche that preclude the action of neutrophils, resulting in immune escape and subsequent fulminant progression of the infection.

microbiology↗

bioRxiv2020

Self-organization and culture of Mesenchymal Stromal Cell spheroids in acoustic levitation

In recent years, 3D cell culture models such as spheroid or organoid technologies have known important developments. Many studies have shown that 3D cultures exhibit better biomimetic properties compared to 2D cultures. These properties are important for in-vitro modeling systems, as well as for in-vivo cell therapies and tissue engineering approaches. A reliable use of 3D cellular models still requires standardized protocols with well-controlled and reproducible parameters. To address this challenge, a robust and scaffold-free approach is proposed, which relies on multi-trap acoustic levitation. This technology is successfully applied to Mesenchymal Stromal Cells (MSCs) maintained in acoustic levitation over a 24-hour period. During the culture, MSCs spontaneously self-organized from cell sheets to cell spheroids with a characteristic time of about ten hours. Each acoustofluidic chip could contain up to 30 spheroids in acoustic levitation and four chips could be ran in parallel, leading to the production of 120 spheroids per experiment. Various biological characterizations showed that the cells inside the spheroids were viable, maintained the expression of their cell surface markers and had a higher differentiation capacity compared to standard 2D culture conditions. These results open the path to long-time cell culture in acoustic levitation of cell sheets or spheroids for any type of cells.

bioengineering↗