Spatio-temporal Dynamics of Immune Cells

Team Publications

Year of publication 2020

Edwards-Jorquera SS, Bosveld F, Bellaïche YA, Lennon-Duménil AM, Glavic Á. (2020 Mar 2)

Trpml controls actomyosin contractility and couples migration to phagocytosis in fly macrophages.

Journal of cell biology : 2 : J Cell Biol. 2020 Mar 2;219(3). pii: e201905228. doi: 10.1083/jcb.201905228. : DOI : 10.1083/jcb.201905228 Learn more
Summary

Phagocytes use their actomyosin cytoskeleton to migrate as well as to probe their environment by phagocytosis or macropinocytosis. Although migration and extracellular material uptake have been shown to be coupled in some immune cells, the mechanisms involved in such coupling are largely unknown. By combining time-lapse imaging with genetics, we here identify the lysosomal Ca2+ channel Trpml as an essential player in the coupling of cell locomotion and phagocytosis in hemocytes, the Drosophila macrophage-like immune cells. Trpml is needed for both hemocyte migration and phagocytic processing at distinct subcellular localizations: Trpml regulates hemocyte migration by controlling actomyosin contractility at the cell rear, whereas its role in phagocytic processing lies near the phagocytic cup in a myosin-independent fashion. We further highlight that Vamp7 also regulates phagocytic processing and locomotion but uses pathways distinct from those of Trpml. Our results suggest that multiple mechanisms may have emerged during evolution to couple phagocytic processing to cell migration and facilitate space exploration by immune cells.

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Edwards-Jorquera SS1, Bosveld F2, Bellaïche YA2, Lennon-Duménil AM3, Glavic Á1. (2020 Mar 2)

Trpml controls actomyosin contractility and couples migration to phagocytosis in fly macrophages.

Journal of cell biology : 219(3) : DOI : 10.1083/jcb.201905228 Learn more
Summary

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Moreau HD1, Lennon-Duménil AM1, Pierobon P1. (2020 Mar 2)

“If you please… draw me a cell”. Insights from immune cells.

Journal of cell science : 133(5) : DOI : 10.1242/jcs.244806 Learn more
Summary

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Year of publication 2019

Stankevicins L, Ecker N, Terriac E, Maiuri P, Schoppmeyer R, Vargas P, Lennon-Duménil AM, Piel M, Qu B, Hoth M, Kruse K, Lautenschläger F. (2020 Jan 14)

Deterministic actin waves as generators of cell polarization cues.

Proceedings of the National Academy of Sciences : 117 : Proc Natl Acad Sci U S A. 2020 Jan 14;117(2):826-835. doi: 10.1073/pnas.1907845117. Epub 2019 Dec 27. : 826,835 : DOI : 10.1073/pnas.1907845117 Learn more
Summary

Dendritic cells “patrol” the human body to detect pathogens. In their search, dendritic cells perform a random walk by amoeboid migration. The efficiency of pathogen detection depends on the properties of the random walk. It is not known how the dendritic cells control these properties. Here, we quantify dendritic cell migration under well-defined 2-dimensional confinement and in a 3-dimensional collagen matrix through recording their long-term trajectories. We find 2 different migration states: persistent migration, during which the dendritic cells move along curved paths, and diffusive migration, which is characterized by successive sharp turns. These states exhibit differences in the actin distributions. Our theoretical and experimental analyses indicate that this kind of motion can be generated by spontaneous actin polymerization waves that contribute to dendritic cell polarization and migration. The relative distributions of persistent and diffusive migration can be changed by modification of the molecular actin filament nucleation and assembly rates. Thus, dendritic cells can control their migration patterns and adapt to specific environments. Our study offers an additional perspective on how dendritic cells tune their searches for pathogens.

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Sáez JJ1,2, Diaz J1, Ibañez J1, Bozo JP1, Cabrera Reyes F1, Alamo M1, Gobert FX3, Obino D3, Bono MR2, Lennon-Duménil AM3, Yeaman C4, Yuseff MI5. (2019 Jul 1)

The exocyst controls lysosome secretion and antigen extraction at the immune synapse of B cells.

Journal of cell biology : 218(7) : :2247-2264 : DOI : 10.1083/jcb.201811131 Learn more
Summary

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Anita Kumari, Judith Pineau, Pablo J Sáez, Mathieu Maurin, Danielle Lankar, Mabel San Roman, Katharina Hennig, Vanessa F Boura, Raphael Voituriez, Mikael C I Karlsson, Martial Balland, Ana-Maria Lennon Dumenil, Paolo Pierobon (2019 Jun 30)

Actomyosin-driven force patterning controls endocytosis at the immune synapse.

Nature communications : 2870 : DOI : 10.1038/s41467-019-10751-7 Learn more
Summary

An important channel of cell-to-cell communication is direct contact. The immune synapse is a paradigmatic example of such type of interaction: it forms upon engagement of antigen receptors in lymphocytes by antigen-presenting cells and allows the local exchange of molecules and information. Although mechanics has been shown to play an important role in this process, how forces organize and impact on synapse function is unknown. We find that mechanical forces are spatio-temporally patterned at the immune synapse: global pulsatile myosin II-driven tangential forces are observed at the synapse periphery while localised forces generated by invadosome-like F-actin protrusions are detected at its centre. Noticeably, we observe that these force-producing actin protrusions constitute the main site of antigen extraction and endocytosis and require myosin II contractility to form. The interplay between global and local forces dictated by the organization of the actomyosin cytoskeleton therefore controls endocytosis at the immune synapse.

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Inoue D1, Obino D2, Pineau J2, Farina F1, Gaillard J1,3, Guerin C1,3, Blanchoin L4,3, Lennon-Duménil AM5, Théry M4,3. (2019 Jun 3)

Actin filaments regulate microtubule growth at the centrosome.

Embo journal : 38(11) : DOI : 10.15252/embj.201899630 Learn more
Summary

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Juan José Sáez, Ana-María Lennon-Duménil, María-Isabel Yuseff (2019 Jun 1)

Studying MHC Class II Presentation of Immobilized Antigen by B Lymphocytes.

Methods in molecular biology (Clifton, N.J.) : 419-437 : DOI : 10.1007/978-1-4939-9450-2_29 Learn more
Summary

The ability of B lymphocytes to capture external antigens (Ag) and present them as peptide fragments, loaded on major histocompatibility complex (MHC) class II molecules, to CD4 T cells is a crucial part of the adaptive immune response. This allows for T-B cooperation, a cellular communication that is required for B cells to develop into germinal centers (GC) and form mature high affinity antibody producing cells and to further develop B cell memory. MHC class II antigen presentation by B lymphocytes is a multistep process involving (1) Recognition and capture of external Ag by B lymphocytes through their B cell receptor (BCR), (2) Ag processing, which comprises the degradation of Ag in internal compartments within the B cell and loading of the corresponding peptide fragments on MHC class II molecules, and (3) Presentation of MHCII-peptide complexes to CD4 T cells. Here, we describe how to study the biochemical and morphological changes that occur in B lymphocytes at these three major levels.

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Hélène D Moreau, Carles Blanch-Mercader, Rafaele Attia, Mathieu Maurin, Zahraa Alraies, Doriane Sanséau, Odile Malbec, Maria-Graciela Delgado, Philippe Bousso, Jean-François Joanny, Raphaël Voituriez, Matthieu Piel, Ana-Maria Lennon-Duménil (2019 Apr 16)

Macropinocytosis Overcomes Directional Bias in Dendritic Cells Due to Hydraulic Resistance and Facilitates Space Exploration.

Developmental cell : 171-188.e5 : DOI : S1534-5807(19)30235-7 Learn more
Summary

The migration of immune cells can be guided by physical cues imposed by the environment, such as geometry, rigidity, or hydraulic resistance (HR). Neutrophils preferentially follow paths of least HR in vitro, a phenomenon known as barotaxis. The mechanisms and physiological relevance of barotaxis remain unclear. We show that barotaxis results from the amplification of a small force imbalance by the actomyosin cytoskeleton, resulting in biased directional choices. In immature dendritic cells (DCs), actomyosin is recruited to the cell front to build macropinosomes. These cells are therefore insensitive to HR, as macropinocytosis allows fluid transport across these cells. This may enhance their space exploration capacity in vivo. Conversely, mature DCs down-regulate macropinocytosis and are thus barotactic. Modeling suggests that HR may help guide these cells to lymph nodes where they initiate immune responses. Hence, DCs can either overcome or capitalize on the physical obstacles they encounter, helping their immune-surveillance function.

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Barbier L1,2,3, Sáez PJ1,2, Attia R1,2, Lennon-Duménil AM4, Lavi I1,2, Piel M1,2, Vargas P1,2. (2019 Apr 12)

Myosin II Activity Is Selectively Needed for Migration in Highly Confined Microenvironments in Mature Dendritic Cells.

Frontiers in immunology : 10 : 747 : DOI : 10.3389/fimmu.2019.00747 Learn more
Summary

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Daisuke Inoue, Dorian Obino, Judith Pineau, Francesca Farina, Jérémie Gaillard, Christophe Guerin, Laurent Blanchoin, Ana-Maria Lennon-Duménil, Manuel Théry (2019 Mar 24)

Actin filaments regulate microtubule growth at the centrosome.

The EMBO journal : DOI : e99630 Learn more
Summary

The centrosome is the main microtubule-organizing centre. It also organizes a local network of actin filaments. However, the precise function of the actin network at the centrosome is not well understood. Here, we show that increasing densities of actin filaments at the centrosome of lymphocytes are correlated with reduced amounts of microtubules. Furthermore, lymphocyte activation resulted in disassembly of centrosomal actin and an increase in microtubule number. To further investigate the direct crosstalk between actin and microtubules at the centrosome, we performed reconstitution assays based on (i) purified centrosomes and (ii) on the co-micropatterning of microtubule seeds and actin filaments. These two assays demonstrated that actin filaments constitute a physical barrier blocking elongation of nascent microtubules. Finally, we showed that cell adhesion and cell spreading lead to lower densities of centrosomal actin, thus resulting in higher microtubule growth. We therefore propose a novel mechanism, by which the number of centrosomal microtubules is regulated by cell adhesion and actin-network architecture.

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Sáez JJ1, Lennon-Duménil AM2, Yuseff MI3. (2019 Jan 1)

Studying MHC Class II Presentation of Immobilized Antigen by B Lymphocytes.

Methods in molecular biology : 1988 : 419-437 : DOI : 10.1007/978-1-4939-9450-2_29 Learn more
Summary

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Year of publication 2018

Dorian Obino, Luc Fetler, Andrea Soza, Odile Malbec, Juan José Saez, Mariana Labarca, Claudia Oyanadel, Felipe Del Valle Batalla, Nicolas Goles, Aleksandra Chikina, Danielle Lankar, Fabián Segovia-Miranda, Camille Garcia, Thibaut Léger, Alfonso Gonzalez, Marion Espéli, Ana-Maria Lennon-Duménil, Maria-Isabel Yuseff (2018 Dec 13)

Galectin-8 Favors the Presentation of Surface-Tethered Antigens by Stabilizing the B Cell Immune Synapse.

Cell reports : 3110-3122.e6 : DOI : S2211-1247(18)31815-1 Learn more
Summary

Complete activation of B cells relies on their capacity to extract tethered antigens from immune synapses by either exerting mechanical forces or promoting their proteolytic degradation through lysosome secretion. Whether antigen extraction can also be tuned by local cues originating from the lymphoid microenvironment has not been investigated. We here show that the expression of Galectin-8-a glycan-binding protein found in the extracellular milieu, which regulates interactions between cells and matrix proteins-is increased within lymph nodes under inflammatory conditions where it enhances B cell arrest phases upon antigen recognition in vivo and promotes synapse formation during BCR recognition of immobilized antigens. Galectin-8 triggers a faster recruitment and secretion of lysosomes toward the B cell-antigen contact site, resulting in efficient extraction of immobilized antigens through a proteolytic mechanism. Thus, extracellular cues can determine how B cells sense and extract tethered antigens and thereby tune B cell responses in vivo.

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Obino D, Fetler L, Soza A, Malbec O, Saez JJ, Labarca M, Oyanadel C, Del Valle Batalla F, Goles N, Chikina A, Lankar D, Segovia-Miranda F, Garcia C, Léger T, Gonzalez A, Espéli M, Lennon-Duménil AM, Yuseff MI. (2018 Dec 11)

Galectin-8 Favors the Presentation of Surface-Tethered Antigens by Stabilizing the B Cell Immune Synapse.

Cell reports : 25(11) : 3110-3122 : DOI : 10.1016/j.celrep.2018.11.052 Learn more
Summary

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Mirjana Weimershaus, François-Xavier Mauvais, Loredana Saveanu, Cézaire Adiko, Joël Babdor, Anastasia Abramova, Sebastian Montealegre, Myriam Lawand, Irini Evnouchidou, Katharina Julia Huber, Alexandra Chadt, Markus Zwick, Pablo Vargas, Michael Dussiot, Ana Maria Lennon-Dumenil, Thomas Brocker, Hadi Al-Hasani, Peter van Endert (2018 Sep 27)

Innate Immune Signals Induce Anterograde Endosome Transport Promoting MHC Class I Cross-Presentation.

Cell reports : 3568-3581 : DOI : S2211-1247(18)31312-3 Learn more
Summary

Both cross-presentation of antigens by dendritic cells, a key pathway triggering T cell immunity and immune tolerance, and survival of several pathogens residing in intracellular vacuoles are intimately linked to delayed maturation of vesicles containing internalized antigens and microbes. However, how early endosome or phagosome identity is maintained is incompletely understood. We show that Toll-like receptor 4 (TLR4) and Fc receptor ligation induces interaction of the GTPase Rab14 with the kinesin KIF16b mediating plus-end-directed microtubule transport of endosomes. As a result, Rab14 recruitment to phagosomes delays their maturation and killing of an internalized pathogen. Enhancing anterograde transport by overexpressing Rab14, promoting the GTP-bound Rab14 state, or inhibiting retrograde transport upregulates cross-presentation. Conversely, reducing Rab14 expression, destabilizing Rab14 endosomes, and inhibiting anterograde microtubule transport by Kif16b knockdown compromise cross-presentation. Therefore, regulation of early endosome trafficking by innate immune signals is a critical parameter in cross-presentation by dendritic cells.

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