Our team has a long-standing interest in professional phagocytes that play a major role in innate and adaptive immune responses. Phagocytosis, the mechanism of capture and degradation of invading microorganisms or debris, is crucial for homeostasis, bacterial clearance and to control the outcome of immune responses. Therefore, it is crucial to understand the mechanisms of phagocytosis, especially of cell debris or microorganisms. We dissect the mechanisms used by phagocytes, in particular the coordinated activities of signaling pathways, membrane trafficking and cytoskeleton dynamics, and their related mechanical constraints, in order to mediate uptake of particulate material (project 1). We are also investigating the related cell activation and the fate of the internalized materials, from the mechanisms of their degradation to their release as non-degraded material that can be recognized by the B lymphocytes (project 2). Additionally, we are deeply interested in understanding how viruses, including HIV-1, Zika virus and respiratory viruses such as the Human Rhinovirus and SARS-Cov2, impair the clearance and activation functions of phagocytes, leading to associated pathologies such as neuronal damage or bacterial superinfections, with a special focus on the role of the type I interferon response (projects 3 and 4).

 

 

 

12 members

3 PhD students

3 patents

4 projects

74 publications

Team news

  • Florence Niedergang was an invited speaker at the "Cell Dynamics Host Pathogen Interface" rescheduled from May 2020 to May 2022 in the UK! Floriane Herit and Suzanne Faure-Dupuy presented a poster and a flash talk.
  • Florence Niedergang was an invited speaker at the "Phagocyte" Gordon Research Conference in April 2022 in the USA and Manon Depierre had a selected talk!
  • Suzanne Faure-Dupuy joined the lab in January 2022 with a FRM "aide au retour en France" post-doctoral fellowship.
  • ANR programmes PhagoChemiForce and NeuroZika started in 2021.

PhD recruitment

Mechanisms of regulation and role of dendritic cell subsets in antigen transfer and activation of B lymphocytes.

Supervisor: Fatah Ouaaz (see project 2)

Dendritic cells (DCs) are professional antigen-presenting cells, which sample antigens (Ags) in the periphery and migrate to the lymph node (LN) where they activate T cells and potentially B cells. Previousely, we have reported that human monocyte-derived DCs were able to store and to release native Ag internalized by macropinocytosis from the late endosomes in the extracellular medium by a process that was named “regurgitation”. Recently, we reported that murine DCs are important peripheral carriers of Ag to the LN B-cell zone and also potent B-cell activators both in vivo and in vitro. Importantly, we highlight that Ag released upon DC regurgitation is sufficient to efficiently induce early B-cell activation through the transcription factor NF-kB/cRel. However, the regulation of DC regurgitation as well as the respective role of the LN-resident DC subsets in Ag transfer and B-cell activation still need to be investigated.

On the basis of these findings, the PhD candidate will now explore: 1) the respective roles of the two distinct LN resident-DC subsets cDC1/CD8a+ and cDC2/CD11b+ in Ag transport, transfer and B-cell activation in vivo and in co-culture in vitro; 2) the mechanisms of regulation and control of DC regurgitation by investigating the role of NF-kB pathway, the intracellular traffic and the B-cell attracting chemokine CXCL-13; 3) Live imaging of Ag transfer from DC subsets to B cells in co-culture in vitro and in vivo.

The candidate will use murine specific anti-HEL B cells (from MD4 transgenic mice) and DCs (bone marrow-derived DCs; ex vivo purified spleen DC subsets) pulsed with Ag (HEL). The candidate will explore the Ag distribution, transfer by DCs and B cell activation in vivo and in co-culture in vitro by multi-color flow cytometry, immunohistochemistry and confocal/2-photon microscopy. The candidate will also measure by ELISA antibody production in mice sera following immunization with HEL-loaded DCs. NF-kB activation will be analyzed after cytosolic / nuclear extracts preparation followed by western blotting and confocal microscopy and its direct role will be approached by a specific chemical inhibition. All experimental approaches are available in the laboratory.

We expect to provide new mechanistic insights into Ag transfer and direct B-cell activation modalities by DCs and also new approaches for NF-kB manipulation and DC targeting for vaccination to elicit humoral immunity.

Contact

Florence Niedergang

22, rue Méchain

75014 Paris

pièce 322

Contact by email