Caspase isoforms in inflammasome activation ...

• Main Author: Digby, Zsofia
• Format: Thesis
• Language: English
• Published: Apollo - University of Cambridge Repository 2020
• Subjects: immunology; innate immunity; inflammasome; Canis lupus
• Online Access: https://dx.doi.org/10.17863/cam.54927; https://www.repository.cam.ac.uk/handle/1810/307833

Inflammasomes are macromolecular signalling platforms composed of a receptor (for example NLRP3 or NLRC4), an adaptor (ASC) and effectors (caspases) that are thought to play critical roles in the host defence against microbial infections. Activation of inflammasomes leads to the processing of the pro-inflammatory cytokines pro-IL-1β and pro- IL-18 to their active form and cleavage of gasdermin D to induce pyroptosis. Caspase-1 is the main inflammatory caspase responsible for cytokine maturation and induction of cell death, while human caspase-4, -5 and the mouse orthologue caspase-11 play an essential role in cytosolic bacterial LPS recognition. The putative importance of inflammasomes suggest that their constituents should be conserved across different animal species, but there are major differences, particularly in the caspase repertoire, in both invertebrates and vertebrates. The dog (Canis lupus familiaris), for example, has a pseudogene for NLRC4 and has a unique caspase-1/4/11 hybrid gene ...