@article{fda188f7fb564a558c0739a8ff902db8,
title = "Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster",
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.",
author = "Naren Srinivasan and Oliver Gordon and Susan Ahrens and Anna Franz and Safia Deddouche and Probir Chakravarty and David Phillips and Yunus, {Ali A.} and Rosen, {Michael K.} and Valente, {Rita S.} and Luis Teixeira and Barry Thompson and Dionne, {Marc S.} and Will Wood and {Reis e Sousa}, Caetano",
note = "Funding Information: We thank Nic Tapon, Paul Martin, Maxine Holder, Georgina Fletcher, Ieva Gailite and members of the Immunobiology Laboratory for helpful discussions and suggestions. We thank the Francis Crick Institute Genomics Equipment Park, Advanced Sequencing Facility, and the Fly facility for assistance. We also thank the Bloomington Stock Centre, the NIG-Fly Stock Center, the Vienna Drosophila Resource Center, and Flybase. This work was supported by The Francis Crick Institute, which receives core funding from Cancer Research UK (FC001136), the UK Medical Research Council (FC001136), and the Wellcome Trust (FC001136), and by Investigator Award WT106973MA from the Wellcome Trust. Wellcome WT106973MA Caetano Reis e Sousa Wellcome FC001136 Caetano Reis e Sousa Medical Research Council FC001136 Caetano Reis e Sousa Cancer Research UK FC001136 Caetano Reis e Sousa The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. Publisher Copyright: {\textcopyright} Srinivasan et al.",
year = "2016",
month = nov,
day = "22",
doi = "10.7554/eLife.19662",
language = "English",
volume = "5",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications Ltd",
number = "NOVEMBER2016",
}