Projets

Multiscale analysis of CD8 T cells responses and modeling

Our goal is to combine in vitro (cell culture) and in vivo (antiviral immune responses) approaches and use multiplex cytometry and single-cell RNA sequencing (Smart-seq2, MARS-seq) to generate data. We seek to model these data in order to characterize the different aspects of the CD8 T lymphocyte response and the generation of memory cells. Two axes are developed:

• Studying the quality of CD8 T cells and their regulatory networks at the single cell level

Memory populations are heterogenous and protective functions may be supported by cellular subsets of memory populations. The objective is to identify, at the single cell level, signatures associated to memory subsets with different effector potential and to decipher the molecular regulatory networks that support their generation.

We aim to establish multiscale models capable of predicting the outcome of immunization protocols in terms of the quality and quantity of memory cells from a few measurable early molecular events.

• Studying the differentiation dynamics of CD8 T cells and the molecular mechanisms behind a form of decision between effector and memory

Various pathways leading to the diversity of effector / memory populations have been described. It is suggested that memory engagement could take place at several stages of the primary immune response. The aim of this project is to study, at the single cell level, the different trajectories followed by naive CD8 T cells to differentiate into memory cells. We also seek to infer their gene networks in order to identify the molecular regulatory mechanisms supporting the trajectories.

Development of new immunotherapeutic approaches against Staphylococcus aureus infections

(in collaboration with EVOTEC, ANAQUANT, CIRI-HCL)

The most commonly identified Gram-positive antibiotic-resistant pathogen in many parts of the world is methicillin-resistant Staphylococcus aureus (MRSA). Bone and joint infections by Staphylococcus aureus are common in joint prostheses and difficult to treat. Their evolution in a chronic form poses major public health problems, with no satisfactory treatments currently available. It is therefore essential to better understand immunity against Staphylococcus aureus and to be able to propose alternative therapeutic or vaccine strategies.

In this context, we are studying the involvement of CD8 T lymphocytes in the protection against chronic Staphylococcus aureus infection. Our project is to evaluate, in established murine models, the therapeutic potential of the CD8 T cytotoxic response against intracellular Staphylococcus aureus (in collaboration with the F. Vandenesh team from CIRI and two industrial partners, ANAQUANT and EVOTEC Gmbh) . This project (ESPRI-IOAC for Eradication, Monitoring, Prediction and Immunotherapy of Complicated Osteo-Articular Infections) is funded by FUI / BPI France (2020-2023)

Characterization of a subpopulation of CD8 memory T cells

Within memory CD8 cells compartment, we distinguish conventional cells ie antigen specific generated in response to a pathogen or a tumor, and so-called innate memory CD8 cells generated via different mechanisms involving strong cytokine stimulation, independently of antigens recognition.

We are interested in a subpopulation of CD8 innate memory cells characterized by the expression of Ly49 markers, classically associated with NK cells. We are studying the development of these cells through the use of transgenic mice deficient for genes involved in thymic selection. In addition, as many studies have demonstrated that these cells could have immunoregulatory properties, we are studying their role during antiviral response.

CIRI COLLABORATIVE PROJECT

Impact of HPV38 E6/E7 oncoproteins on the immune response to allergens

The skin is in constant contact with its environment and is therefore constantly exposed to physical damage resulting from its interaction with microorganisms and environmental factors such as UV radiation or exposure to chemicals. Our project aims to understand how two environmental factors can interact to cause inflammatory skin pathology. Skin colonization by human papillomavirus (HPV), a virus widely distributed in humans, alters the skin's immune response in response to UV radiation and contributes to the development of skin carcinoma. The molecular mechanisms involved in this synergy can be studied in an original preclinical model, where the E6 / E7 genes of the virus are expressed in keratinocytes. We will use this model to study the impact of these viral proteins on the skin's response to chemicals that induce inflammatory pathologies. The demonstration of a synergy will pave the way for epidemiological studies in humans to determine whether certain types of HPV virus can promote the development of inflammatory skin pathologies.

Equipes/Teams : “Immunity and Cytotoxic CD8 lymphocytes” and “Immunology of skin allergy and vaccination”