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
Figure 1: Immunofluorescence by confocal microscopy of macrophages infected by HIV-1. Nucleus (violet), actin (light blue) tubulin (red), Gag (green)
Figure 2: Live imaging by confocal microscopy of human primary macrophages infected by HIV-1 (in green) and transduced by Life-act cherry.
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).