Autophagie, Infections et Immunité

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Thèmes de recherche

Our team studies the role of macroautophagy in basic immunity and immunopathologies, especially in the context of infections. Macroautophagy, referred to as autophagy, is an essantial lysosomal catabolic pathway : Christian de Duve, who discovered the role of lysosomes in autophagy and coined the word « autophagy » (for self-eating), and Yoshinori Ohsumi, who identified the first autophagy-related genes, were both congratulated by a Nobel Prize in 1974 and 2016, respectively, highlighting the importance of this cellular process in Medicine and Physiology.

Autophagy allows the sequestration of large portions of the cytoplasm within double-membraned vesicles called autophagosomes. Subsequently of the fusion of autophagosomes with lysosomes, the cytoplasmic content is degraded within autolysosomes. In mammalian cells, regulation of autophagy involves dozens of proteins including those of the ATG (AuTphaGy-related) family. Essential for the maintenance of cellular homeostasis, autophagy is also a cell-autonomous defense mechanism that allows each cell to fight intracellular pathogens (viruses, bacteria or parasites), by targeting them towards a lysosomal degradation. In addition, autophagy contributes to the regulation of innate (type I interferon synthesis, inflammation, cell death…) and adaptive (peptide presentation on major histocompatibility molecules) immune responses, by facilitating their development in response to an infection. Thus, autophagy appears to be central for the establishment of an immediate as well as a long-term immune response against infectious agents. However, many pathogens have evolved molecular strategies in order to escape or hijack autophagy to facilitate their replication.

Disruption of autophagy is associated with many human diseases such as neurodegenerative diseases, cancer, inflammatory diseases or infectious diseases. Among others, genomic analyses have revealed a high association between Crohn’s Disease (a chronic intestinal inflammatory disorder affecting around 1 million people in Europe) susceptibility and polymorphisms affecting autophagy-associated genes.

Our scientific objective is to get a better understanding of the selective autophagy process in the context of infections and immunity, and to develop also translational projects to get benefit from our knowledge in fundamental autophagy/immunology in the understanding of the human inflammatory disorder of the intestine, in particular in Crohn’s Disease.

Beyond, our team is highly involved in teaching activities/responsibilities, in Licence, Masters and Doctoral School (UCBL1 & ENS-L), in clinic (Gastroenterology Hospital Lyon-Sud), and contributes to the development of well-organized cohorts of patients, and is involved in several scientific council/networks (CFATG, REMIND, GETAID …).

 

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