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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...

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Autores principales: Srinivasan, Naren, Gordon, Oliver, Ahrens, Susan, Franz, Anna, Deddouche, Safia, Chakravarty, Probir, Phillips, David, Yunus, Ali A, Rosen, Michael K, Valente, Rita S, Teixeira, Luis, Thompson, Barry, Dionne, Marc S, Wood, Will, Reis e Sousa, Caetano
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5138034/
https://www.ncbi.nlm.nih.gov/pubmed/27871362
http://dx.doi.org/10.7554/eLife.19662
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author Srinivasan, Naren
Gordon, Oliver
Ahrens, Susan
Franz, Anna
Deddouche, Safia
Chakravarty, Probir
Phillips, David
Yunus, Ali A
Rosen, Michael K
Valente, Rita S
Teixeira, Luis
Thompson, Barry
Dionne, Marc S
Wood, Will
Reis e Sousa, Caetano
author_facet Srinivasan, Naren
Gordon, Oliver
Ahrens, Susan
Franz, Anna
Deddouche, Safia
Chakravarty, Probir
Phillips, David
Yunus, Ali A
Rosen, Michael K
Valente, Rita S
Teixeira, Luis
Thompson, Barry
Dionne, Marc S
Wood, Will
Reis e Sousa, Caetano
author_sort Srinivasan, Naren
collection PubMed
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. DOI: http://dx.doi.org/10.7554/eLife.19662.001
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spelling pubmed-51380342016-12-07 Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster Srinivasan, Naren Gordon, Oliver Ahrens, Susan Franz, Anna Deddouche, Safia Chakravarty, Probir Phillips, David Yunus, Ali A Rosen, Michael K Valente, Rita S Teixeira, Luis Thompson, Barry Dionne, Marc S Wood, Will Reis e Sousa, Caetano eLife Immunology 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. DOI: http://dx.doi.org/10.7554/eLife.19662.001 eLife Sciences Publications, Ltd 2016-11-22 /pmc/articles/PMC5138034/ /pubmed/27871362 http://dx.doi.org/10.7554/eLife.19662 Text en © 2016, Srinivasan et al http://creativecommons.org/licenses/by/4.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Immunology
Srinivasan, Naren
Gordon, Oliver
Ahrens, Susan
Franz, Anna
Deddouche, Safia
Chakravarty, Probir
Phillips, David
Yunus, Ali A
Rosen, Michael K
Valente, Rita S
Teixeira, Luis
Thompson, Barry
Dionne, Marc S
Wood, Will
Reis e Sousa, Caetano
Actin is an evolutionarily-conserved damage-associated molecular pattern that signals tissue injury in Drosophila melanogaster
title 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_short 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
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5138034/
https://www.ncbi.nlm.nih.gov/pubmed/27871362
http://dx.doi.org/10.7554/eLife.19662
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