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

Naren 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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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 number19662
Number of pages25
JournaleLIFE
Volume5
Early online date22 Nov 2016
DOIs
Publication statusE-pub ahead of print - 22 Nov 2016

Keywords

  • DENDRITIC CELL-RECEPTOR
  • HUMORAL STRESS-RESPONSE
  • SYSTEMIC WOUND RESPONSE
  • JAK/STAT PATHWAY
  • INFLAMMATORY RESPONSE
  • IMMUNE-RESPONSES
  • IN-VIVO
  • SUPEROXIDE-DISMUTASE
  • RNA INTERFERENCE
  • TYROSINE KINASE

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