Drosophila caspases as guardians of host-microbe interactions

An intact cell death machinery is not only crucial for successful embryonic development and tissue homeostasis, but participates also in the defence against pathogens and contributes to a balanced immune response. Centrally involved in the regulation of both cell death and inflammatory immune responses is the evolutionarily conserved family of cysteine proteases named caspases. The Drosophila melanogaster genome encodes for seven caspases, several of which display dual functions, participating in apoptotic signalling and beyond. Among the Drosophila caspases, the caspase-8 homologue Dredd has a well-characterised role in inflammatory signalling activated by bacterial infections, and functions as a driver of NF-κB-mediated immune responses. Regarding the other Drosophila caspases, studies focusing on tissue-specific immune signalling and host-microbe interactions have recently revealed immunoregulatory functions of the initiator caspase Dronc and the effector caspase Drice. The aim of this review is to give an overview of the signalling cascades involved in the Drosophila humoral innate immune response against pathogens and of their caspase-mediated regulation. Furthermore, the apoptotic role of caspases during antibacterial and antiviral immune activation will be discussed. [Image: see text]