Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster
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...
Main Authors: | , , , , , , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
eLife Sciences Publications Ltd
2016-11-01
|
Series: | eLife |
Subjects: | |
Online Access: | https://elifesciences.org/articles/19662 |
id |
doaj-fe2f27a79c6945b9a55b17fd85b0bd6b |
---|---|
record_format |
Article |
spelling |
doaj-fe2f27a79c6945b9a55b17fd85b0bd6b2021-05-05T00:42:31ZengeLife Sciences Publications LtdeLife2050-084X2016-11-01510.7554/eLife.19662Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogasterNaren Srinivasan0Oliver Gordon1https://orcid.org/0000-0002-2567-2482Susan Ahrens2Anna Franz3Safia Deddouche4Probir Chakravarty5David Phillips6Ali A Yunus7Michael K Rosen8https://orcid.org/0000-0002-0775-7917Rita S Valente9Luis Teixeira10https://orcid.org/0000-0001-8326-6645Barry Thompson11https://orcid.org/0000-0002-0103-040XMarc S Dionne12https://orcid.org/0000-0002-8283-1750Will Wood13Caetano Reis e Sousa14https://orcid.org/0000-0001-7392-2119Immunobiology Laboratory, The Francis Crick Institute, London, United KingdomImmunobiology Laboratory, The Francis Crick Institute, London, United KingdomImmunobiology Laboratory, The Francis Crick Institute, London, United KingdomDepartment of Biochemistry, Biomedical Sciences, University Walk, University of Bristol, Bristol, United KingdomImmunobiology Laboratory, The Francis Crick Institute, London, United KingdomBioinformatics, The Francis Crick Institute, London, United KingdomGenomics-Equipment Park, The Francis Crick Institute, London, United KingdomDepartment of Biophysics, University of Texas Southwestern Medical Center, Dallas, United StatesDepartment of Biophysics, University of Texas Southwestern Medical Center, Dallas, United StatesInstituto Gulbenkian de Ciência, Oeiras, PortugalInstituto Gulbenkian de Ciência, Oeiras, PortugalEpithelial Biology Laboratory, The Francis Crick Institute, London, United KingdomDepartment of Life Sciences and MRC Centre for Molecular Bacteriology and Infection, South Kensington Campus, Imperial College London, London, United KingdomDepartment of Cellular and Molecular Medicine, Biomedical Sciences, University of Bristol, Bristol, United KingdomImmunobiology Laboratory, The Francis Crick Institute, London, United KingdomDamage-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.https://elifesciences.org/articles/19662innate immunitydamage-associated molecular patterntissue injuryJAK/STAT pathwayDAMPsterile inflammation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Naren Srinivasan Oliver Gordon Susan Ahrens Anna Franz Safia Deddouche Probir Chakravarty David Phillips Ali A Yunus Michael K Rosen Rita S Valente Luis Teixeira Barry Thompson Marc S Dionne Will Wood Caetano Reis e Sousa |
spellingShingle |
Naren Srinivasan Oliver Gordon Susan Ahrens Anna Franz Safia Deddouche Probir Chakravarty David Phillips Ali A Yunus Michael K Rosen Rita S Valente Luis Teixeira Barry Thompson Marc S Dionne Will Wood Caetano Reis e Sousa Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster eLife innate immunity damage-associated molecular pattern tissue injury JAK/STAT pathway DAMP sterile inflammation |
author_facet |
Naren Srinivasan Oliver Gordon Susan Ahrens Anna Franz Safia Deddouche Probir Chakravarty David Phillips Ali A Yunus Michael K Rosen Rita S Valente Luis Teixeira Barry Thompson Marc S Dionne Will Wood Caetano Reis e Sousa |
author_sort |
Naren Srinivasan |
title |
Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster |
title_short |
Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster |
title_full |
Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster |
title_fullStr |
Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster |
title_full_unstemmed |
Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster |
title_sort |
actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in drosophila melanogaster |
publisher |
eLife Sciences Publications Ltd |
series |
eLife |
issn |
2050-084X |
publishDate |
2016-11-01 |
description |
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. |
topic |
innate immunity damage-associated molecular pattern tissue injury JAK/STAT pathway DAMP sterile inflammation |
url |
https://elifesciences.org/articles/19662 |
work_keys_str_mv |
AT narensrinivasan actinisanevolutionarilyconserveddamageassociatedmolecularpatternthatsignalstissueinjuryindrosophilamelanogaster AT olivergordon actinisanevolutionarilyconserveddamageassociatedmolecularpatternthatsignalstissueinjuryindrosophilamelanogaster AT susanahrens actinisanevolutionarilyconserveddamageassociatedmolecularpatternthatsignalstissueinjuryindrosophilamelanogaster AT annafranz actinisanevolutionarilyconserveddamageassociatedmolecularpatternthatsignalstissueinjuryindrosophilamelanogaster AT safiadeddouche actinisanevolutionarilyconserveddamageassociatedmolecularpatternthatsignalstissueinjuryindrosophilamelanogaster AT probirchakravarty actinisanevolutionarilyconserveddamageassociatedmolecularpatternthatsignalstissueinjuryindrosophilamelanogaster AT davidphillips actinisanevolutionarilyconserveddamageassociatedmolecularpatternthatsignalstissueinjuryindrosophilamelanogaster AT aliayunus actinisanevolutionarilyconserveddamageassociatedmolecularpatternthatsignalstissueinjuryindrosophilamelanogaster AT michaelkrosen actinisanevolutionarilyconserveddamageassociatedmolecularpatternthatsignalstissueinjuryindrosophilamelanogaster AT ritasvalente actinisanevolutionarilyconserveddamageassociatedmolecularpatternthatsignalstissueinjuryindrosophilamelanogaster AT luisteixeira actinisanevolutionarilyconserveddamageassociatedmolecularpatternthatsignalstissueinjuryindrosophilamelanogaster AT barrythompson actinisanevolutionarilyconserveddamageassociatedmolecularpatternthatsignalstissueinjuryindrosophilamelanogaster AT marcsdionne actinisanevolutionarilyconserveddamageassociatedmolecularpatternthatsignalstissueinjuryindrosophilamelanogaster AT willwood actinisanevolutionarilyconserveddamageassociatedmolecularpatternthatsignalstissueinjuryindrosophilamelanogaster AT caetanoreisesousa actinisanevolutionarilyconserveddamageassociatedmolecularpatternthatsignalstissueinjuryindrosophilamelanogaster |
_version_ |
1721476217657360384 |