Phagocyte Architecture and Dynamics


Our team combines cutting-edge techniques in optical and electron imaging, material science, cell mechanics and intra-vital imaging to elucidate how phagocytes, in particular macrophages and osteoclasts, interact with the extracellular matrix, to decipher the mechanisms of macrophage 3D migration and investigate how HIV-1 manipulates phagocyte cell-to-cell spread.
In the long term, our projects will allow the identification of new targets to control the interactions of macrophages with their environment, which will be valuable against both cancer and HIV infection.


We investigate how phagocytes interact with their microenvironment, in physiological and pathological contexts including cancer and infectious diseases.

Macrophages are innate immune cells that migrate and are present in all tissues to maintain the immune surveillance. They are targets for pathogens and ingest particles such as bacteria or dead cells, a process called phagocytosis. Our team focuses on the mechanisms used by macrophages to interact with their environments, in order to reveal molecules that could be usefully targeted to limit their deleterious action.

Using intravital microscopy, our team revealed that macrophages use the mesenchymal mode of migration to infiltrate dense tumors and that inhibitors of matrix metalloproteases both decreased the number of tumor-associated macrophages and tumor growth (Gui et al. 2018 Cancer Immunol Res). Podosomes are cell adhesion structures involved in the degradation of the extracellular matrix and the mesenchymal migration of macrophages. They are composed of a submicron core of actin filaments surrounded by a ring of integrin-based adhesion complexes.

Thanks to a method that we called protrusion force microscopy, we demonstrated that podosomes generate protrusive forces that are proportional to the stiffness of the extracellular matrix (Labernadie et al. 2014 Nat Commun; Proag et al. 2015 ACS Nano; Labernadie et al. 2022 Nat Commun), and involve a balance of forces between core protrusion and a traction at the adhesion ring (Bouissou et al. 2017 ACS Nano). In bone degrading osteoclasts, podosomes assemble into a super structure called the sealing zone, and we could show using super-resultion microscopy techniques that there is a local coordination of podosome cores within micrometer-scale islets (Portes et al. 2022 Elife). We also developed a device combining microchannels and pillars and reported that forces are redirected from inwards to outwards with increased cell confinement (Desvignes et al. 2018 Nano Lett). More recently, we could demonstrate, in close collaboration with Marion Jasnin and Serge Dmitrieff, that nano-scale forces by podosomes can be explained by the elastic energy stored in podosome actin networks (Jasnin et al. 2022 Nat Commun).

We showed that the HIV-1 protein Nef modulates the migration of macrophages both in vitro and in vivo, and favors virus dissemination by enhancing the mesenchymal migration and by modulating podosome structure and function (Vérollet et al. 2015 Blood). In addition, we observed that osteoclasts are productively infected by HIV-1. The virus strongly alters podosome organization in osteoclasts, leading to enhanced bone resorption activity (Raynaud-Messina et al. 2018 PNAS). These observations likely explain macrophage accumulation in several tissues of HIV-1 infected patients and why they suffer from osteolysis. Macrophages are also the main host cells for Mycobacterium tuberculosis (Mtb). In the context of tuberculosis, we reported that macrophage mesenchymal migration is enhanced, and associated with an accumulation of Mtb-permissive macrophages in lungs (Lastrucci et al. 2015 Cell Res). We also showed that, in tuberculosis microenvironment, the formation of tunneling nanotubes (TNT) by macrophages is increased. When these macrophages are subsequently infected by HIV-1 the virus spread between cells using TNT and the lectin Siglec-1/CD169. These mechanisms could explain how tuberculosis enhances HIV-1 pathogenesis in co-infected patients (Souriant et al. 2019 Cell Rep; Dupont et al. 2020 Elife; Dupont et al. 2022 J Leuk Biol). More recently, we revealed a novel and efficient mechanism of tissue macrophage infection by HIV-1 via the fusion with infected CD4 T lymphocytes (Mascarau et al. 2023 J Cell Biol).


Team members

Research Scientists

Fabrice Dumas (University)
Arnaud Labrousse (University)
Véronique Le Cabec (CNRS)
Renaud Poincloux (CNRS)
Brigitte Raynaud-Messina (CNRS)
Christel Vérollet (Inserm)

Research Engineer

Ugo Arles
Adeline Girel
Arnaud Métais (CNRS)

Post-doctoral Fellow

Javier Ray-Barroso

PhD Students

Océane Dewingle
Natacha Faivre
Camille Gorlt
Sarah Monard
Marianna Plozza

Our research projects

Mascarau M et al. (2023) Productive HIV-1 infection of tissue macrophages by fusion with infected CD4+ T cells. J Cell Biol

Portes M et al. (2022) Nanoscale architecture and coordination of actin cores within the sealing zone of human osteoclasts. Elife

Jasnin M et al. (2022) Elasticity of dense actin networks produces nanonewton protrusive forces.
Nat Commun

Dupont M et al. (2020) Tuberculosis-associated IFN-I induces Siglec-1 on tunneling nanotubes and favors HIV-1 spread in macrophages. Elife

Souriant S et al. (2019) Tuberculosis exacerbates HIV-1 infection through IL-10/STAT3-dependent tunneling nanotube formation in macrophages. Cell Rep

Raynaud-Messina B et al. (2018) The bone degradation machinery of osteoclasts: a novel HIV-1 target that contributes to bone loss. Proc Natl Acad Sci USA

Scanning electron micrography of human monocyte-derived macrophages (pink) that have infiltrated a thick layer of Matrigel® (grey) for 72h. They degrade the extracellular matrix and dig tunnels. © Renaud Poincloux