Project Details
Abstract
Cytolethal distending toxin (CDT), a member of the genotoxin family, is associated with Campylobacter jejuni-induced enterocolitis. CDT holotoxin composes three toxin subunits: CdtA, CdtB, and CdtC. The interaction of CdtA/CdtC with membrane lipid rafts is essential for CdtB internalization and trafficking in the cells. Noticeably, CdtB possesses type-I deoxyribonuclease activity that causes DNA double-strand break (DSB), resulting in cell death. Necroptosis is a new type of programmed necrosis, which purposefully promote the secretion of considerable damage-associated molecular patterns (DAMPs). Since our current studies found that CDT-induced inflammasome is mediated through necroptosis, we posit that necroptosome is the sensor mainly for this context. Despite the evidence pointing to the involvement of necroptosis in CDT-induced pathogenesis, there are still many missing pieces. Therefore, three specific aims are raised herein, including: (i) investigating how CDT is delivered to the cytoplasmic compartments; (ii) exploring CDT-induced necroptosis to enhance DAMP-driven inflammation; (iii) studying the role of lipid rafts in CDT-triggered necroptosome signaling. This study will unveil the detailed mechanism by which CDT manipulates necroptosome and, in particular, the consequences for the host immune response against bacterial infection.
Project IDs
Project ID:PC10907-1704
External Project ID:MOST109-2320-B182-025-MY3
External Project ID:MOST109-2320-B182-025-MY3
Status | Finished |
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Effective start/end date | 01/08/20 → 31/07/21 |
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