Abstract
Damage associated molecular patterns (DAMPs) are released by dead cells and can 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 evolution of adaptive immunity.
Article and author information
Author details
Funding
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.
Reviewing Editor
- Zhijian J Chen, University of Texas Southwestern Medical School, United States
Publication history
- Received: July 14, 2016
- Accepted: November 14, 2016
- Accepted Manuscript published: November 22, 2016 (version 1)
- Version of Record published: December 5, 2016 (version 2)
- Version of Record updated: December 19, 2016 (version 3)
Copyright
© 2016, Srinivasan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 3,169
- Page views
-
- 851
- Downloads
-
- 24
- Citations
Article citation count generated by polling the highest count across the following sources: Scopus, Crossref, PubMed Central.