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The Circulating Protease Persephone Is an Immune Sensor for Microbial Proteolytic Activities Upstream of the Drosophila Toll Pathway

Microbial or endogenous molecular patterns as well as pathogen functional features can activate innate immune systems. Whereas detection of infection by pattern recognition receptors has been investigated in details, sensing of virulence factors activities remains less characterized. In Drosophila,...

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Autores principales: Issa, Najwa, Guillaumot, Nina, Lauret, Emilie, Matt, Nicolas, Schaeffer-Reiss, Christine, Van Dorsselaer, Alain, Reichhart, Jean-Marc, Veillard, Florian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823974/
https://www.ncbi.nlm.nih.gov/pubmed/29452635
http://dx.doi.org/10.1016/j.molcel.2018.01.029
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author Issa, Najwa
Guillaumot, Nina
Lauret, Emilie
Matt, Nicolas
Schaeffer-Reiss, Christine
Van Dorsselaer, Alain
Reichhart, Jean-Marc
Veillard, Florian
author_facet Issa, Najwa
Guillaumot, Nina
Lauret, Emilie
Matt, Nicolas
Schaeffer-Reiss, Christine
Van Dorsselaer, Alain
Reichhart, Jean-Marc
Veillard, Florian
author_sort Issa, Najwa
collection PubMed
description Microbial or endogenous molecular patterns as well as pathogen functional features can activate innate immune systems. Whereas detection of infection by pattern recognition receptors has been investigated in details, sensing of virulence factors activities remains less characterized. In Drosophila, genetic evidences indicate that the serine protease Persephone belongs to a danger pathway activated by abnormal proteolytic activities to induce Toll signaling. However, neither the activation mechanism of this pathway nor its specificity has been determined. Here, we identify a unique region in the pro-domain of Persephone that functions as bait for exogenous proteases independently of their origin, type, or specificity. Cleavage in this bait region constitutes the first step of a sequential activation and licenses the subsequent maturation of Persephone to the endogenous cysteine cathepsin 26-29-p. Our results establish Persephone itself as an immune receptor able to sense a broad range of microbes through virulence factor activities rather than molecular patterns.
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spelling pubmed-58239742018-02-27 The Circulating Protease Persephone Is an Immune Sensor for Microbial Proteolytic Activities Upstream of the Drosophila Toll Pathway Issa, Najwa Guillaumot, Nina Lauret, Emilie Matt, Nicolas Schaeffer-Reiss, Christine Van Dorsselaer, Alain Reichhart, Jean-Marc Veillard, Florian Mol Cell Article Microbial or endogenous molecular patterns as well as pathogen functional features can activate innate immune systems. Whereas detection of infection by pattern recognition receptors has been investigated in details, sensing of virulence factors activities remains less characterized. In Drosophila, genetic evidences indicate that the serine protease Persephone belongs to a danger pathway activated by abnormal proteolytic activities to induce Toll signaling. However, neither the activation mechanism of this pathway nor its specificity has been determined. Here, we identify a unique region in the pro-domain of Persephone that functions as bait for exogenous proteases independently of their origin, type, or specificity. Cleavage in this bait region constitutes the first step of a sequential activation and licenses the subsequent maturation of Persephone to the endogenous cysteine cathepsin 26-29-p. Our results establish Persephone itself as an immune receptor able to sense a broad range of microbes through virulence factor activities rather than molecular patterns. Cell Press 2018-02-15 /pmc/articles/PMC5823974/ /pubmed/29452635 http://dx.doi.org/10.1016/j.molcel.2018.01.029 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Issa, Najwa
Guillaumot, Nina
Lauret, Emilie
Matt, Nicolas
Schaeffer-Reiss, Christine
Van Dorsselaer, Alain
Reichhart, Jean-Marc
Veillard, Florian
The Circulating Protease Persephone Is an Immune Sensor for Microbial Proteolytic Activities Upstream of the Drosophila Toll Pathway
title The Circulating Protease Persephone Is an Immune Sensor for Microbial Proteolytic Activities Upstream of the Drosophila Toll Pathway
title_full The Circulating Protease Persephone Is an Immune Sensor for Microbial Proteolytic Activities Upstream of the Drosophila Toll Pathway
title_fullStr The Circulating Protease Persephone Is an Immune Sensor for Microbial Proteolytic Activities Upstream of the Drosophila Toll Pathway
title_full_unstemmed The Circulating Protease Persephone Is an Immune Sensor for Microbial Proteolytic Activities Upstream of the Drosophila Toll Pathway
title_short The Circulating Protease Persephone Is an Immune Sensor for Microbial Proteolytic Activities Upstream of the Drosophila Toll Pathway
title_sort circulating protease persephone is an immune sensor for microbial proteolytic activities upstream of the drosophila toll pathway
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5823974/
https://www.ncbi.nlm.nih.gov/pubmed/29452635
http://dx.doi.org/10.1016/j.molcel.2018.01.029
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