Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogasterMore about Open Access at the Crick
Authors listNaren 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 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 orthologue of Syk, and Src42A, a 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.