Vascular Cell Biology in Infection Inflammation and Cancer
Our team has a long-standing interest in vascular cell biology in the context of infection and inflammation, in particular at the central nervous system level, where the blood-brain barrier tightly controls neuronal environment. Vascular endothelial cells are major targets of sepsis-induced events. A wide range of invasive pathogens directly target endothelial cells and affect most aspects of endothelial cell biology, leading to edema, occlusive clotting, excessive inflammation and organ failure. Among them, Neisseria meningitidis (meningococcus) is still a leading cause of two rare but devastating invasive diseases: meningitis and severe sepsis (purpura fulminans).
We have developed interdisciplinary approaches to elucidate the intricated network of interactions and molecular strategies elicited by this bacterial pathogen to colonize human vasculature, promote vascular dysfunction, immune escape and get access to the brain. Our original research led to the identification of innovative therapeutic strategies to combat bacteria-induced severe endothelial dysfunction. We identified compounds against Type IV pili, a major meningococcal virulence factor required to promote vascular colonization and subsequent vascular alterations. Type IV are also found in numerous bacterial pathogens and contribute to their pathogenesis. More recently, we identified a potent vascular stabilization factor conferring vascular protection against severe sepsis.
We have expertise in vascular biology, blood-brain barrier, cell culture under flow, meningococcal and pneumococcal infection, live cell imaging, high resolution imaging (STORM), RNA seq, tissue analysis. We have an immortalized cell line of human brain microvascular endothelial cells (hCMEC/D3), now distributed in more than 300 laboratories worldwide, and a humanized mouse model of skin infection (SCID mice grafted wth human skin).
1- Endothelial cell biomarkers in critically ill COVID-19 patients with encephalitis. Altmayer V, Ziveri J et al. J Neurochem. 2021 Nov 25. doi: 10.1111/jnc.15545.
2- The minor pilin PilV provides a conserved adhesion site throughout the antigenically variable meningococcal type IV pilus. Barnier JP et al. Proc Natl Acad Sci U S A. (2021);118:e2109364118.
3- Receptor recognition by meningococcal type IV pili relies on a specific complex N-glycan. Le Guennec L et al. Proc Natl Acad Sci U S A., (2020) 117 (5) 2606-2612.
4- Targeting Type IV pili as an antivirulence strategy against invasive meningococcal disease. Denis K et al.
Nature Microbiol, (2019) 4:972-984.
5- Strength of Neisseria meningitidis binding to endothelial cells requires highly-ordered CD147/β2-adrenoceptor clusters assembled by alpha-Actinin-4. Maïssa N et al. Nature Commun (2017) 1;8:15764
Dernières publications sur HAL :
- [hal-02152777] Targeting Type IV pili as an antivirulence strategy against invasive meningococcal diseaseby email@example.com (Kevin Denis) on 24 October 2023 at 16h11
Bacterial virulence factors are attractive targets for the development of therapeutics. Type IV pili, which are associated with a remarkable array of […]
- [hal-03552862] Meningococcal disease: A paradigm of type‐IV pilus dependent pathogenesisby firstname.lastname@example.org (Mathieu Coureuil) on 15 February 2022 at 14h56
Neisseria meningitidis (meningococcus) is a Gram-negative bacterium responsible for two devastating forms of invasive diseases: purpura fulminans and […]
- [hal-03552815] The minor pilin PilV provides a conserved adhesion site throughout the antigenically variable meningococcal type...by email@example.com (Jean-Philippe Barnier) on 15 February 2022 at 13h58
Neisseria meningitidis utilizes type IV pili (T4P) to adhere to and colonize host endothelial cells, a process at the heart of meningococcal invasive […]
- [hal-03552952] Pathogenic Neisseria meningitidis utilizes CD147 for vascular colonizationby firstname.lastname@example.org (Sandra C Bernard) on 15 February 2022 at 13h56
Neisseria meningitidis is a cause of meningitis epidemics worldwide and of rapidly progressing fatal septic shock. A crucial step in the pathogenesis […]