Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster
- The Francis Crick Institute, United Kingdom
- Voisin Consulting Life Sciences, United Kingdom
- University of Bristol, United Kingdom
- Sanofi Strasbourg, France
- University of Texas Southwestern Medical Center, United States
- Instituto Gulbenkian de Ciência, Portugal
- Imperial College London, United Kingdom
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.
Data availability
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Genome-wide responses to extracellular actinPublicly available at the NCBI Gene Expression Omnibus (accession no: GSE76150).
Article and author information
Author details
Caetano Reis e Sousa
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
Version 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.
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Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster
eLife 5:e19662.
https://doi.org/10.7554/eLife.19662
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