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

Srinivasan N, O Gordon, S Ahrens, Anna Franz, S Deddouche, P Chakravarty, D Phillips, AA Yunus, MK Rosen, RS Valente, L Teixeira, B Thompson, MS Dionne, Will Wood, Caetano Reis e Sousa

Research output: Contribution to journalArticle (Academic Journal)peer-review

25 Citations (Scopus)
238 Downloads (Pure)

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.

Original languageEnglish
Article numbere19662
Number of pages25
JournaleLife
Volume5
DOIs
Publication statusPublished - 22 Nov 2016

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