TY - JOUR
T1 - Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster
AU - N, Srinivasan
AU - Gordon, O
AU - Ahrens, S
AU - Franz, Anna
AU - Deddouche, S
AU - Chakravarty, P
AU - Phillips, D
AU - Yunus, AA
AU - Rosen, MK
AU - Valente, RS
AU - Teixeira, L
AU - Thompson, B
AU - Dionne, MS
AU - Wood, Will
AU - e Sousa, Caetano Reis
PY - 2016/11/22
Y1 - 2016/11/22
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85005950521&partnerID=8YFLogxK
U2 - 10.7554/eLife.19662
DO - 10.7554/eLife.19662
M3 - Article (Academic Journal)
C2 - 27871362
AN - SCOPUS:85005950521
VL - 5
JO - eLife
JF - eLife
SN - 2050-084X
M1 - e19662
ER -