Autophagy, Infections & Immunity

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Research themes

Our research projects aim to study the role of macroautophagy in the immune system, especially in the context of infections. Macroautophagy, referred to as autophagy, is a lysosomal catabolic pathway. It 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, disruption of autophagy is associated with many human diseases such as neurodegenerative diseases, cancer, inflammatory diseases or infectious diseases.
Indeed, autophagy is 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.

Our work aims at understanding how autophagy contributes to the pathogen control, and how some pathogens manipulate autophagy.

This project was initiated with Prof. Chantal Rabourdin-Combe (1952-2011).

Main achievements

  • We described the first human pathogen receptor which induces autophagy via a selective molecular pathway (2009).
  • We described the interactome between proteins that regulate autophagy and viral proteins. We identified common autophagic proteins which are targeted by several viruses known  to subvert autophagy (measles virus, HIV-1, HCV) (2011).

Sponsors

Institut Universitaire de France (IUF), ARC, Ligue Contre le Cancer, LabEx ECOFECT, FINOVI, INSERM.

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