Phagocytosis and Signaling
Oliver Nüsse (Professor), Hadrien Jalaber (Research Assistant)
Alumni: Sophie Dupré-Crochet (Professor at UVSQ since 2023), Salomé Laurans (PhD Candidate 2020–2024), Alexandra Zak (PhD Candidate 2016–2019), Jérémy Joly (PhD Candidate 2016–2019), Elodie Hudik (Research Assistant)
Our goal is to understand the intracellular signaling that controls phagocytosis and the spatiotemporal organization of NADPH oxidase assembly at the phagosome using fluorescence video microscopy in differentiated PLB-985 cells (neutrophil-like) [Tlili2012 ; Faure2013, Song2017]. We investigate the intracellular signaling regulating these events, focusing on the role of anionic phospholipids, such as phosphoinositides and phosphatidylserine, which are emerging as potential regulators [Song2017, Song2020]. Our work has shown that the duration of NADPH oxidase activation in the phagosome is closely linked to the prolonged presence of PI3P. Through super-resolution microscopy (dSTORM), we observed significant aggregation of NADPH oxidase membrane components at the phagosomal membrane. A portion of Nox2 transits through the endocytic pathway [Joly2020].
Co-localization of Nox2 and Rab11, a marker of recycling endosomes, in a PLB-985 cell [Joly2020], scale bar = 3 µm.
We are also interested in the membrane physics during phagocytosis. In response to mechanical stress such as phagocytosis, this induces rapid changes in the viscoelastic properties of the membrane [Zak2021]. This distinctly affects membrane extension and stiffness of the cell [Zak2022] , and we are currently investigating the causes.
The role of neutrophils in eliminating bacteria and fungi is well known, but their interactions with viruses have been less studied. Neutrophils can be essential for resolving viral infections but, in some cases, may become overactivated, causing significant damage to host tissues (e.g., SARS-CoV-2). Among the viruses encountered by neutrophils, adenoviruses are responsible for mild infections. However, certain serotypes can cause severe infections. Adenoviruses are also used as vectors for vaccines or in anti-cancer therapy. In collaboration with the Institut Gustave Roussy, we study the interaction between neutrophils and adenoviruses, and the consequences of these interactions for both the phagocytes and the virus.
A PLB-985 cell held by a pipette (left) attempts to internalize an opsonized bead held by a second pipette. The displacement of the latter allows us to measure the forces involved and deduce the cell's stiffness and elasticity [Zak2021], scale bar = 5 µm