Team leader

Dr. Thierry Rabilloud, DR2 CNRS, HDR Phone: 04 38 78 32 12

The research team develops three interconnected themes, in addition to technological developments for proteomics, running as a background project. The central project deals with the responses of myeloid cells to metallic ions and nanoparticles, and two other projects are connected to it. One project deals with the responses of the bacterium Bacillus subtilis to metallic ions and nanoparticles and also uses a combination of proteomic and targeted approaches. The third project is centered on molecular studies in radio-induced inflammation, with a focus on the effects of different types of radiation sources in this process.​

Research project

An important part of the team studies how metallic ions and metallic oxides impact cells. For example, there is a clear relationship between various diseases and the phagocytosis of toxic (nano)particulate material by myeloid cells including macrophages, which are highly phagocytic. This is for example the case for asbestos and mesotheliomas, silica and silicosis, and this is also highly suspected for at least part of the toxic effects of tobacco smoke or diesel particles.
This relation is due to the primary scavenging function of some myeloid cells such as macrophages. When such cells phagocyte particles, they try to degrade them in their lysosomes. This can lead to the liberation of toxics adsorbed on the phagocytized particles. In the case of metal-containing particles, the toxics can be heavy metal ions or transition metal ions that will be dissolved by the acidic conditions prevailing in the lysosome. Besides such toxic effects, macrophage activation following phagocytosis of particulate material also results in the production of pro-inflammatory mediators, and this inflammation, if it becomes chronic, can be part of the etiology of some diseases such as cancer. Some of these factors are known, such as TNF, IL-6 or IL-12, but the complete scope of these proteins is not known yet.
There is thus a high interest to understand how myeloid cells and especially macrophages react to particles, and especially to metal containing nanoparticles, as well as the corresponding metallic ions. Our project goes beyond the simple observation of toxic effects, and aims at providing molecular mechanisms for a better understanding of the effects of these agents. Classically, this type of research is carried out by focused approaches on targets selected on the basis of previous knowledge; we will not neglect such approaches. However, we also believe that proteomics can deliver significant knowledge, owing to its wide and unbiased scope. Indeed, some work exists in this direction, either on the toxicity of metallic ions or on the effects of metallic oxide particles.
This mixed targeted-wide scope combination of approaches is also used when studying the responses of the soil bacterium Bacillus subtilis to nanoparticles, as this bacterium has an important ecotoxicological role.
Last but not least, the theme centered on radio-induced inflammation studies how exposure of healthy or cancer cells to a wide range of radiation doses affects their inflammatory response, and how this response can modulate their immune micro-environment. Work is also performed to identify the cellular factors involved in the production of these mediators.​


Research actions

       Proteomics study of the effects of metals on cells

In this subproject, we study by proteomics the effects of metal ions and metallic particles on myeloid cells and on bacteria.
To investigate the effects of metallic particles and ions by proteomics, we use the same staggered strategy that we have used to investigate the differentiation of these cells. First, we will perform a comparative proteomics analysis at the scale of whole cell extracts. In this case, the fact that proteomics mainly shows the cellular stress response proteins will not be a problem, as this is exactly what we want to investigate, i.e. the details of the stress response that is made by the cells under the various conditions tested. Depending on the context and on the molecular responses revealed by this first stage, we can perform other proteomic studies (e.g. secretome, metalloproteomics via affinity chromatography).

       Targeted studies

While proteomics offer the power of large scale and unbiased studies, its requirements in terms of sample consumption and its limitations in the analysis of lower abundance proteins does not make it a suitable tool for the detailed analysis of precise phenomena, especially for in vivo studies where the sample resources are often limited. This is why we also carry out targeted studies on the response of cells to various stimuli, including metals. As the scope of such studies can be overwhelmingly high, we use the know-how present in the team. These targeted studies can be focused on certain classes of molecules (e.g. cytokines, inflammasome), on core function of the macrophages (e.g. phagocytosis) or be used as a validation of the mechanisms highlighted by the proteomic analyses. Technically speaking, these studies use biochemistry as well as flow cytometry or qRT-PCR. As an example, our recent work on copper oxide nanoparticles drove us to investigate mitochondrial proteins and glutathione biosynthesis (Triboulet et al., Molecular and Cellular Proteomics, 2013).

       Radiobiology: Inflammation and Cellular Response to Radiation

Irradiation always affects immune cells, whether they are circulating or tissue-resident. In addition to leukopenia, irradiation triggers an inflammatory reaction to restore tissue homeostasis. However, if this inflammation is not controlled, it can become deleterious (Lumniczky, Environ. Int., 2021).

Cellular Specificity and Mechanisms

The mechanisms of radiation-induced inflammation remain poorly understood. It is not for example established whether all cell types respond in the same way to different types of exposures.

Our work shows that the transcription of genes coding for inflammatory factors varies according to the cell type and the type of irradiation:

• No clear inflammatory profile in primary fibroblasts and keratinocytes, but their secretions influence _bystander_ blood cells (Testard, J. Rad. Res., 2013).
• Early and transient inflammatory response in endothelial cells exposed to high doses of radiation, dependent on ATM and NF-kB (Rouichi, Rad Res, 2025).
• The dose and LET (Linear Energy Transfer) of radiation, and the mode of irradiation (dose rate, spatial fractionation) influence the response (unpublished data).

Our current work focuses on the role of modifying factors such as obesity and sex hormones in modulating radiation-induced inflammation in mammary epithelial cells, in relation to an increased risk of breast cancer (Pianoforte/MIRAMARE project).

We are also studying the modulation of the inflammatory response of cancer cells in vitro (Césaire, Mol. Cell. Biochem., 2026) and in patients treated with radiotherapy (Frey, Strahlenther. Onkol., 2020), in relation to cell radioresistance and treatment modalities.

Impact on the Immune System

Irradiation causes leukopenia. Our work contributes to the characterization of the dynamics of T lymphocytes (Mika, Cell. Mol. Life Sci., 2017) and other leukocytes (Pham, Radiother. Oncol., 2025) in murine models after whole-body or brain irradiation.

We also participate in the work of the ImmgenT consortium on the development of the T lymphocyte repertoire in mice (Jaquish, Nature Immunol., 2025).

Technology for proteomics

We are also deeply implicated in technological projects aiming at improving the performances of the proteomics toolbox, especially in the field of protein separation. We strongly believe that proteomics must continue to deal with complete proteins with their associated post-translational modifications, and cannot be reduced only to the study of digestion peptides, with the associated loss of filiation between the proteins and the peptides. We are thus working in the field of protein solubilization prior to electrophoresis, on the improvement of the electrophoretic methods per se, on the field of protein detection after gel and also on dedicated sample preparation methods fpr specific classes of proteins electrophoresis (see the associated bibliography of the team).

Insertion in the national and international context

Our team is part of several national and international networks and initiatives relevant to its research themes, such as the national Labex SERENADE (study of nanoparticles), the Labex PRIMES (focused on radiotherapy), the European platform MELODI (research on the effects of low radiation doses), the EURATOM Pianoforte partnership (MIRAMARE project, on the risk of radiation-induced cancer), and the Imm​genT consortium (biology of T lymphocytes in mice).