Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster

Journal Article: eLifeYear Published: (2016) Volume Number: 5, Article Number: e19662


Srinivasan,Naren; Gordon,Oliver; Ahrens,Susan; Franz,Anna; Deddouche,Safia; Chakravarty,Probir; Phillips,David; Yunus,Ali A; Rosen,Michael K; Valente,Rita S; Teixeira,Luis; Thompson,Barry; Dionne,Marc S; Wood,Will; Reis e Sousa,Caetano

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.