Epithelial Memory to Candida albicans during commensalism and infection

Descripción del proyecto

Desvelar la memoria epitelial en la inmunidad fúngica

«Candida albicans», un hongo que suele residir en la boca, puede causar infecciones cuando se altera el equilibrio del sistema inmunitario. Una regulación precisa ayuda a controlar su transición de comensal a microorganismo patógeno. Mientras que las células inmunitarias innatas desarrollan respuestas a largo plazo frente a las infecciones, el papel de las células epiteliales orales (CEO) en la regulación del crecimiento fúngico no se conoce del todo. Las CEO son cruciales para la respuesta inmunitaria en la boca, donde las células inmunitarias son limitadas. El equipo del proyecto EPIMemory, que cuenta con el apoyo de las Acciones Marie Skłodowska-Curie, pretende descubrir cómo la memoria de las células epiteliales orales CEO controla las infecciones por «C. albicans» y el equilibrio microbiano. Mediante el análisis de la expresión génica y los perfiles metabólicos, en el proyecto se pretende identificar dianas terapéuticas para potenciar la inmunidad de las mucosas y mejorar los tratamientos.

Objetivo

In this research project I seek to discover the mechanisms underlying oral epithelial cell (OEC) memory and its importance to control Candida albicans infections and commensalism. C. albicans is part of the healthy microbiota, but it is also the most clinically relevant fungus. Fine tuning of mucosal immunity enables homeostasis and regulates commensal-to-pathogen transition of C. albicans. Innate immune cells, such as macrophages, can develop long-term responses during systemic infections, enabling them to clear invading microbes more efficiently. This so-called process of “innate immune memory” can be targeted in order to improve patient outcomes. However, at the oral mucosa, where immune cells are more scarce, OECs are essential for controlling fungal growth and orchestrating complex immune responses. Whilst OEC-C. albicans interactions have been well analysed during acute infections, no study up to date has addressed epithelial memory or its impact on fighting fungal infections and regulating Candida commensalism.
The aim of this project is to understand the molecular and cellular mechanisms driving epithelial memory in response to C. albicans. In preliminary in vitro studies, I have shown that epithelial memory protects OECs from C. albicans and therefore, I hypothesised that this phenomenon control fungal growth during pathogenesis and homeostasis. I will use advanced models of host-microbe interactions to confirm the importance of epithelial memory for clearing infections and whether it promotes fungal commensalism by regulating microbial growth. I will decipher the underlying molecular mechanisms by analysing gene expression and metabolic profiles of memory cells, and identify potential targets that promote homeostasis at the oral mucosa.
This project will yield novel insights into mucosal fungal immunology, essential knowledge to further comprehend how out body interacts with the microbiota and to identify targets to advance in the treatment of candidiasis.