Deciphering how the interplay between dysbiosis and MAIT cells impacts skin repair – IMMUNESTA

Barrier sites are colonized with microbiota and are populated by innate and adaptive immune cells. Host immune system is involved in constant dialogue with commensal microorganisms while preventing pathogen entry. This interplay becomes critical during chronic wounds, which is correlated with persistent inflammation and colonization by an altered microbiota called skin dysbiosis. Our hypothesis is that Staphylococcus aureus (Sa), the main bacterium implicated in skin dysbiosis, plays a major role in delayed wound healing by interfering with the functions of specific immune cells, including mucosal-associated invariant T (MAIT) cells, which is one of the major T cell population in skin. To test this hypothesis, we will rely on a paradigmatic disease model of chronic non-healing wounds associated with Sa-dominated skin dysbiosis, the recessive dystrophic epidermolysis bullosa (RDEB). Our consortium, composed of three complementary partners in the field of inflammation and microbiota, proposes to divide our project into three major work packages: WP1 - Defining the microbial and immunological signatures of chronic wounds in patients with RDEB to identify bacterial factors responsible for delayed wound healing; WP2 – Identification of bacterial factors responsible for delayed wound healing through in vitro modelling; WP3 - To better define the interactions between microbiota, skin epithelial cells and immune cells in chronic wounds using mouse chronic wound infection models. This project is unique and original and our preliminary data with samples from RDEB patients confirm the feasibility of the project, the expertise of the teams, and their effective collaboration.