elife-19662-v3.pdf (2.09 MB)
Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster
journal contributionposted on 2020-10-02, 14:09 authored by Naren Srinivasan, Oliver Gordon, Susan Ahrens, Anna Franz, Safia Deddouche, Probir Chakravarty, David Phillips, Ali A Yunus, Michael K Rosen, Rita S Valente, Luis Teixeira, Barry Thompson, Marc S Dionne, Will Wood, Caetano Reis e Sousa
Damage-associated molecular patterns (DAMPs) are molecules released by dead cells that trigger sterile inflammation and, in vertebrates, adaptive immunity. Actin is a DAMP detected in mammals by the receptor, DNGR-1, expressed by dendritic cells (DCs). DNGR-1 is phosphorylated by Src-family kinases and recruits the tyrosine kinase Syk to promote DC cross-presentation of dead cell-associated antigens. Here we report that actin is also a DAMP in invertebrates that lack DCs and adaptive immunity. Administration of actin to Drosophila melanogaster triggers a response characterised by selective induction of STAT target genes in the fat body through the cytokine Upd3 and its JAK/STAT-coupled receptor, Domeless. Notably, this response requires signalling via Shark, the Drosophila orthologue of Syk, and Src42A, a Drosophila Src-family kinase, and is dependent on Nox activity. Thus, extracellular actin detection via a Src-family kinase-dependent cascade is an ancient means of detecting cell injury that precedes the evolution of adaptive immunity.
D. melanogasterDAMPJAK/STAT pathwaydamage-associated molecular patternimmunologyinnate immunitysterile inflammationtissue injuryActinsAlarminsAnimalsDrosophila melanogasterSignal TransductionStress, PhysiologicalReis e Sousa FC001136Thompson FC001180CBGEPAS-ackFLY-ack0601 Biochemistry and Cell Biology