TY - JOUR TI - Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster AU - Srinivasan, Naren AU - Gordon, Oliver AU - Ahrens, Susan AU - Franz, Anna AU - Deddouche, Safia AU - Chakravarty, Probir AU - Phillips, David AU - Yunus, Ali A AU - Rosen, Michael K AU - Valente, Rita S AU - Teixeira, Luis AU - Thompson, Barry AU - Dionne, Marc S AU - Wood, Will AU - Reis e Sousa, Caetano A2 - Chen, Zhijian J VL - 5 PY - 2016 DA - 2016/11/22 SP - e19662 C1 - eLife 2016;5:e19662 DO - 10.7554/eLife.19662 UR - https://doi.org/10.7554/eLife.19662 AB - 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. KW - innate immunity KW - damage-associated molecular pattern KW - tissue injury KW - JAK/STAT pathway KW - DAMP KW - sterile inflammation JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -