Mycolactone, a pathogen-derived inhibitor of Sec61 with immunosuppressive properties
Event details
| Date | 08.08.2018 |
| Hour | 10:30 › 11:30 |
| Speaker | Jean-David Morel, Immunobiology of Infection Unit, Institut Pasteur, Paris, France |
| Location | |
| Category | Conferences - Seminars |
SEMINAR of the LAUSANNE INTEGRATIVE METABOLISM and NUTRITION ALLIANCE (LIMNA)
Abstract:
Mycolactone is a diffusible macrolide produced by the human pathogen Mycobacterium ulcerans, the causative agent of necrotic skin lesions called Buruli ulcers. In addition to displaying cytotoxic properties locally, mycolactone down-regulates the host immune responses. In vitro work had indicated that mycolactone blocks the co-translational translocation of secretory proteins into the endoplasmic reticulum (ER), leading to their cytosolic degradation by the ubiquitin:proteasome system. We demonstrated that mycolactone targets the alpha subunit of the Sec61 translocon (Sec61α). Using quantitative proteomics, we showed that Sec61 blockade impairs key immune processes, such as antigen presentation by dendritic cells, T cell activation and migration. These global analyses also revealed that mycolactone-driven Sec61 blockade triggers ER stress responses, eventually causing apoptotic cell death.
(*) IMPORTANT NOTICE: All external participants have to pass through SV Reception/Welcome Desk to be able to access to AI 1153. Contact person to call at arrival at SV Reception Desk: Administrative Assistant (ext. 3 95 22).
Abstract:
Mycolactone is a diffusible macrolide produced by the human pathogen Mycobacterium ulcerans, the causative agent of necrotic skin lesions called Buruli ulcers. In addition to displaying cytotoxic properties locally, mycolactone down-regulates the host immune responses. In vitro work had indicated that mycolactone blocks the co-translational translocation of secretory proteins into the endoplasmic reticulum (ER), leading to their cytosolic degradation by the ubiquitin:proteasome system. We demonstrated that mycolactone targets the alpha subunit of the Sec61 translocon (Sec61α). Using quantitative proteomics, we showed that Sec61 blockade impairs key immune processes, such as antigen presentation by dendritic cells, T cell activation and migration. These global analyses also revealed that mycolactone-driven Sec61 blockade triggers ER stress responses, eventually causing apoptotic cell death.
(*) IMPORTANT NOTICE: All external participants have to pass through SV Reception/Welcome Desk to be able to access to AI 1153. Contact person to call at arrival at SV Reception Desk: Administrative Assistant (ext. 3 95 22).
Practical information
- Informed public
- Free
Organizer
- Johan Auwerx on behalf of the Lausanne Integrative Metabolism and Nutrition Alliance - LIMNA