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  • U932 – Immunity and Cancer
  • Myeloid Cells and Immunity
U932 St Feliu 2018-2_long

Myeloid Cells and Immunity

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Philippe

Philippe Benaroch Team Leader Tel:

Myeloid cells probably represent the most ancient form of cellular immunity against pathogens and tumor cells. Myeloid cells are very plastic, endowed with an ever-growing list of functions in innate and adaptive immunity.

How activation and polarization of myeloid cells is regulated, how they crosstalk with pathogens, such as viruses, or tumor cells remains to be established at the molecular level and represent the focus of the lab.

As models, we study human myeloid cells, their interactions with a virus that targets them (HIV), and their crosstalk with tumor cells. We also investigate how the activation of an innate sensor is regulated in myeloid cells, and how it impacts on anti-viral and anti-tumoral immune responses. Our goal is to decipher the molecular mechanisms involved in the regulation of the various functions of the myeloid compartment.

Our research can be split into 3 main axes:

1) We analyze how HIV interacts with primary macrophages and dendritic cell subsets. We focus on particular aspects of the viral life cycle in these different cell subsets, and the responses it induces. Such studies not only bring knowledge on HIV infection but also reveal new functions of human myeloid subsets. Figures 1 and 2

2) We study the regulation of macrophage and dendritic cell activation by Nucleic acid sensors, which are key sentinels of the innate immune system. We analyze in particular how one of these sensors is tightly regulated at the post-translational level and how its activation can shape myeloid cell fates.

3) We investigate the crosstalk between myeloid and tumor cells in 3-Dimensional co-culture systems, to best mimic the situation in vivo and to decipher the impact of this crosstalk on both cell types. We also develop ways to manipulate the myeloid compartment to improve the anti-tumor immune response. Figure 3

 

fig 1 benaroch

Figure 1: Immunofluorescence by confocal microscopy of macrophages infected by HIV-1. Nucleus (violet), actin (light blue) tubulin (red), Gag (green)

fig 2 benaroch

Figure 2: Live imaging by confocal microscopy of human primary macrophages infected by HIV-1 (in green) and transduced by Life-act cherry.

fig 3 benaroch

Figure 3: Imaging hetero-spheroids by epifluorescence microscopy. 2500 KP-GFP lung tumor cells (in green) and 5000 mouse monocytes (in red) were co-cultured for several days. The nuclei are stained with dapi (in blue).

Key publications

Year of publication 2017

Jérémie Decalf, Marion Desdouits, Vasco Rodrigues, François-Xavier Gobert, Matteo Gentili, Santy Marques-Ladeira, Célia Chamontin, Marylène Mougel, Bruna Cunha de Alencar, Philippe Benaroch (2017 May 12)

Sensing of HIV-1 Entry Triggers a Type I Interferon Response in Human Primary Macrophages.

Journal of virology : DOI : e00147-17

Year of publication 2013

Stefano Berre, Raphaël Gaudin, Bruna Cunha de Alencar, Marion Desdouits, Mélanie Chabaud, Nadia Naffakh, Marc Rabaza-Gairi, François-Xavier Gobert, Mabel Jouve, Philippe Benaroch (2013 Oct 21)

CD36-specific antibodies block release of HIV-1 from infected primary macrophages and its transmission to T cells.

The Journal of experimental medicine : 2523-38 : DOI : 10.1084/jem.20130566
Raphaël Gaudin, Bruna Cunha de Alencar, Nathalie Arhel, Philippe Benaroch (2013 Apr 8)

HIV trafficking in host cells: motors wanted!

Trends in cell biology : 652-62 : DOI : 10.1016/j.tcb.2013.09.004

Year of publication 2012

Raphaël Gaudin, Bruna Cunha de Alencar, Mabel Jouve, Stefano Bèrre, Emmanuel Le Bouder, Michael Schindler, Aditi Varthaman, François-Xavier Gobert, Philippe Benaroch (2012 Oct 22)

Critical role for the kinesin KIF3A in the HIV life cycle in primary human macrophages.

The Journal of cell biology : 467-79 : DOI : 10.1083/jcb.201201144
Alejandra Garcia-Cattaneo, François-Xavier Gobert, Mélanie Müller, Florent Toscano, Marcella Flores, Aurianne Lescure, Elaine Del Nery, Philippe Benaroch (2012 May 18)

Cleavage of Toll-like receptor 3 by cathepsins B and H is essential for signaling.

Proceedings of the National Academy of Sciences of the United States of America : 9053-8 : DOI : 10.1073/pnas.1115091109

Year of publication 2009

Matias Ostrowski, Nuno B Carmo, Sophie Krumeich, Isabelle Fanget, Graça Raposo, Ariel Savina, Catarina F Moita, Kristine Schauer, Alistair N Hume, Rui P Freitas, Bruno Goud, Philippe Benaroch, Nir Hacohen, Mitsunori Fukuda, Claire Desnos, Miguel C Seabra, François Darchen, Sebastian Amigorena, Luis F Moita, Clotilde Thery (2009 Aug 14)

Rab27a and Rab27b control different steps of the exosome secretion pathway.

Nature cell biology : 19-30; sup pp 1-13 : DOI : 10.1038/ncb2000
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Keywords

HIV, innate sensing, Macrophages, Toll like receptors, virus assembly, virus escape

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