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

Autor: 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
Jazyk: angličtina
Rok vydání: 2016
Předmět:
Zdroj: eLife, Vol 5 (2016)
Druh dokumentu: article
ISSN: 2050-084X
DOI: 10.7554/eLife.19662
Popis: 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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