The metabolic and endocrine role of adipose tissue (AT) is established. The AT is composed mainly of adipocytes but also of immune cells, best known for controlling the metabolic homeostasis of the tissue. The immune activity of TA is associated with the secretion of cytokines and metabolites that modulate its immune function. Obesity, characterized by an accumulation of AT at the subcutaneous or visceral level, is associated with the local inflammation of AT. However, the AT can be infected by different pathogens and it constitutes a site of accumulation of CD8 T lymphocytes (TL) specific for them, which protect against reinfection. These data therefore encourage us to investigate the interactions between adipocytes and CD8-TL in the AT.
The project will be carried out in the CoVir team, which is developing various projects aimed at deciphering the anti-infectious properties of adipose tissue. It is part of a consortium established for an ANR project (INSERM, CNRS, Institut Pasteur de Lille). The objective of the team's project is to study the local contribution of adipocytes and CD8-TL residing in the TA during influenza virus infection in a non-human primate (NHP) model. The NHP presents metabolic and immune responses similar to humans. In addition to in-vivo approaches in NHP, we will develop a 3D co-culture model to target the interaction between adipocytes and CD8-TL, without interference from inflammatory and metabolic signals external to TA. This project benefits from the historical expertise developed in the institute (IMVA-HB UMR 1184/I IDMIT, directed by R. Le Grand) concerning the study of viral infections in the preclinical model of PNH. IDMIT platforms provide equipment and expertise in histology, cytometry (LFC), cytokine/chemokine detection (L2I) and animal welfare (ASW).
The thesis project will focus on in vitro approaches. We will compare the interactions between adipocytes and LT, by studying the metabolic and immune response of each of these fractions. Indeed, adipocyte cells exhibit strong metabolic activity but exert their own immune activity (through the production of microbicidal peptides) and immunomodulatory activity. Concerning immune cells, their functional activity is dependent on their metabolic functions and it is crucial to evaluate the immune-metabolic modifications of immune cells in the presence of adipocytes. The organoid model will allow us to evaluate : (i) the impact of the context of obesity to those in a context of metabolic normality, (ii) the impact of viral pathogens on each of these two fractions. In the medium term, this model will make it possible to test strategies for modulating TA functions during metabolic pathologies or viral infections.