| RRC ID |
47274
|
| 著者 |
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.
|
| タイトル |
Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster.
|
| ジャーナル |
Elife
|
| 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.
|
| 巻・号 |
5
|
| 公開日 |
2016-11-22
|
| DOI |
10.7554/eLife.19662
|
| PII |
e19662
|
| PMID |
27871362
|
| PMC |
PMC5138034
|
| MeSH |
Actins / metabolism*
Alarmins / metabolism*
Animals
Drosophila melanogaster / physiology*
Signal Transduction
Stress, Physiological*
|
| IF |
7.08
|
| 引用数 |
21
|
| リソース情報 |
| ショウジョウバエ |
18247R-2
18247R-3 |
