MISTRAL

Consequences of reciprocal control of mistranslation during antifungal immunity (MISTRAL), defines a novel exploratory research axis at the interface of cell biology and immunology, which aims at understanding the cross-talk between the innate microbial sensing cascades and the change in the fidelity of mRNA translation. We will focus on dendritic cells (DCs), which orchestrate the immune response, and the human fungal pathogen Candida albicans, which display unusual immune-modulatory properties. Contrary to what is commonly believed, mRNA translation fidelity is altered significantly during stress and pathogen detection. The consequences of mistranslation are multiple, and could be beneficial for both the infected cells and the pathogen. Mistral aims at: i) Identifying and design accurate methods to quantify mistranslation. ii) Identifying molecules and pathways involved and regulating in mistranslation. iii) Defining the reciprocal consequences of mistranslation for both the host and pathogens. MISTRAL will explore the consequences of tRNA modifications and tRNA modifying enzymes regulated expression in Yeast and in DCs during microbial detection. We will demonstrate how Candida albicans uses mistranslation to potentiate survival, adaption and evade immune cells. While, DCs and macrophages could use mistranslation to boost anti-fungal immunity through the generation of cryptic antigenic epitopes and inflammatory cytokine production. MISTRAL will combined multidisciplinary approaches, based on the assembled consortium’s extended scientific expertise in cell biology, immunology and yeast genetics and is supported by an array of preliminary data and innovative tools already obtained in collaboration between the University of Aveiro and the Center for Immunology of Marseille-Luminy.