Srinivasan, N; Gordon, O; Ahrens, S; Franz, A; Deddouche, S; Chakravarty, P; Phillips, D; ... Reis e Sousa, C; + view all Srinivasan, N; Gordon, O; Ahrens, S; Franz, A; Deddouche, S; Chakravarty, P; Phillips, D; Yunus, AA; Rosen, MK; Valente, RS; Teixeira, L; Thompson, B; Dionne, MS; Wood, W; Reis e Sousa, C; - view fewer (2016) Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster. eLife , 5 , Article e19662. 10.7554/eLife.19662.

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Abstract

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.

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