Nicolas Matt, PhD. Group leader at UPR 9022 – M3i CNRS
Contact
Nicolas Matt
Phone
E-Mail
Website
UPR 9022 – M3I CNRS
Institut de Biologie Moléculaire et Cellulaire du CNRS
2 allée Konrad Roentgen
67084 Strasbourg Cedex
France
Research topics
- Transcriptional network induced upon pathogen specific infection
- RNA-Protein interaction, translational control and regulation of transcription
Role in NetRNA
The aim of our research is to decipher the complex regulatory network underlying the innate immune response. Through the understanding of specific RNA-protein interaction during transcription and translation of NF-kB induced target genes, we expect to understand the molecular basis of selectivity in the innate immune response both in Drosophila and in mammals.
Working Group
Publications
2018
Issa, N; Guillaumot, N; Lauret, E; Matt, N; Schaeffer-Reiss, C; Dorsselaer, A Van; Reichhart, J M; Veillard, F
The Circulating Protease Persephone Is an Immune Sensor for Microbial Proteolytic Activities Upstream of the Drosophila Toll Pathway Journal Article
In: Mol Cell, vol. 69, no. 4, pp. 539-550 e6, 2018, ISBN: 29452635, (1097-4164 (Electronic) 1097-2765 (Linking) Journal Article Research Support, Non-U.S. Gov't).
@article{nokey,
title = {The Circulating Protease Persephone Is an Immune Sensor for Microbial Proteolytic Activities Upstream of the Drosophila Toll Pathway},
author = {N Issa and N Guillaumot and E Lauret and N Matt and C Schaeffer-Reiss and A Van Dorsselaer and J M Reichhart and F Veillard},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=29452635},
doi = {10.1016/j.molcel.2018.01.029},
isbn = {29452635},
year = {2018},
date = {2018-01-01},
journal = {Mol Cell},
volume = {69},
number = {4},
pages = {539-550 e6},
abstract = {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.},
note = {1097-4164 (Electronic)
1097-2765 (Linking)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {},
pubstate = {published},
tppubtype = {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.
Issa, N; Guillaumot, N; Lauret, E; Matt, N; Schaeffer-Reiss, C; Dorsselaer, A Van; Reichhart, J M; Veillard, F
The Circulating Protease Persephone Is an Immune Sensor for Microbial Proteolytic Activities Upstream of the Drosophila Toll Pathway Journal Article
In: Mol Cell, vol. 69, no. 4, pp. 539-550 e536, 2018, ISBN: 29452635, (1097-4164 (Electronic) 1097-2765 (Linking) Journal Article Research Support, Non-U.S. Gov't).
@article{nokey,
title = {The Circulating Protease Persephone Is an Immune Sensor for Microbial Proteolytic Activities Upstream of the Drosophila Toll Pathway},
author = {N Issa and N Guillaumot and E Lauret and N Matt and C Schaeffer-Reiss and A Van Dorsselaer and J M Reichhart and F Veillard},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=29452635},
doi = {10.1016/j.molcel.2018.01.029},
isbn = {29452635},
year = {2018},
date = {2018-01-01},
journal = {Mol Cell},
volume = {69},
number = {4},
pages = {539-550 e536},
abstract = {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.},
note = {1097-4164 (Electronic)
1097-2765 (Linking)
Journal Article
Research Support, Non-U.S. Gov't},
keywords = {},
pubstate = {published},
tppubtype = {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.
2017
Chamy, L El; Matt, N; Reichhart, J M
Advances in Myeloid-Like Cell Origins and Functions in the Model Organism Drosophila melanogaster Journal Article
In: Microbiol Spectr, vol. 5, no. 1, 2017, ISBN: 28102122, (2165-0497 (Electronic) 2165-0497 (Linking) Journal Article Review Research Support, Non-U.S. Gov't).
@article{nokey,
title = {Advances in Myeloid-Like Cell Origins and Functions in the Model Organism Drosophila melanogaster},
author = {L El Chamy and N Matt and J M Reichhart},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=28102122},
doi = {10.1128/microbiolspec.MCHD-0038-2016},
isbn = {28102122},
year = {2017},
date = {2017-01-01},
journal = {Microbiol Spectr},
volume = {5},
number = {1},
abstract = {Drosophila has long served as a valuable model for deciphering many biological processes, including immune responses. Indeed, the genetic tractability of this organism is particularly suited for large-scale analyses. Studies performed during the last 3 decades have proven that the signaling pathways that regulate the innate immune response are conserved between Drosophila and mammals. This review summarizes the recent advances on Drosophila hematopoiesis and immune cellular responses, with a particular emphasis on phagocytosis.},
note = {2165-0497 (Electronic)
2165-0497 (Linking)
Journal Article
Review
Research Support, Non-U.S. Gov't},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Drosophila has long served as a valuable model for deciphering many biological processes, including immune responses. Indeed, the genetic tractability of this organism is particularly suited for large-scale analyses. Studies performed during the last 3 decades have proven that the signaling pathways that regulate the innate immune response are conserved between Drosophila and mammals. This review summarizes the recent advances on Drosophila hematopoiesis and immune cellular responses, with a particular emphasis on phagocytosis.
Koltun, B; Shackelford, E; Bonnay, F; Matt, N; Reichhart, J M; Orian, A
The SUMO-targeted ubiquitin ligase, Dgrn, is essential for Drosophila innate immunity Journal Article
In: Int J Dev Biol, vol. 61, no. 3-4-5, pp. 319-327, 2017, ISBN: 28621429, (1696-3547 (Electronic) 0214-6282 (Linking) Journal Article).
@article{nokey,
title = {The SUMO-targeted ubiquitin ligase, Dgrn, is essential for Drosophila innate immunity},
author = {B Koltun and E Shackelford and F Bonnay and N Matt and J M Reichhart and A Orian},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=28621429},
doi = {10.1387/ijdb.160250ao},
isbn = {28621429},
year = {2017},
date = {2017-01-01},
journal = {Int J Dev Biol},
volume = {61},
number = {3-4-5},
pages = {319-327},
abstract = {The ability of metazoans to combat pathogenic infection involves both systemic and local responses to the invading pathogens. Ubiquitin and SUMO pathways molecularly regulate the response to infection, immune signaling and gene expression. Here, we report that Degringolade (Dgrn, CG10981), a SUMO-targeted ubiquitin ligase connecting the two pathways, is essential for the innate immunity response in Drosophila. dgrn(DK) null and heterozygous mutant adult flies are severely immune-compromised and succumb rapidly to both pathogenic bacteria and fungi infections. The sensitivity to infection stems from the inability to produce multiple anti-microbial peptides, and transcriptional analyses suggest that the overexpression of Dgrn enhances the transcriptional output of the NF-ĸB related Toll and immune deficiency (IMD)-pathways. Moreover, expression of Dgrn alleviated the inhibitory impact of the cytoplasmic NF-ĸB inhibitor Cactus and the nuclear co-repressor Groucho/TLE (Gro). Additionally, we found that Dgrn is required for the local regenerative response of the mid-gut following infection. Upon oral infection, dgrn mutant flies fail to activate the Delta-Notch pathway in stem cells and enteroblasts, and are unable to regenerate and replace the damaged and dying enterocytes. Interestingly, the ubiquitin-specific protease CG8334 (dUSP32/dUSP11) antagonizes Dgrn activity in the gut, and halving the dose of CG8334 restores Delta-Notch signaling and rescues the lethality observed in dgrn mutants. Collectively, our data suggest that Dgrn is essential for both systemic and local tissue response to infection.},
note = {1696-3547 (Electronic)
0214-6282 (Linking)
Journal Article},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The ability of metazoans to combat pathogenic infection involves both systemic and local responses to the invading pathogens. Ubiquitin and SUMO pathways molecularly regulate the response to infection, immune signaling and gene expression. Here, we report that Degringolade (Dgrn, CG10981), a SUMO-targeted ubiquitin ligase connecting the two pathways, is essential for the innate immunity response in Drosophila. dgrn(DK) null and heterozygous mutant adult flies are severely immune-compromised and succumb rapidly to both pathogenic bacteria and fungi infections. The sensitivity to infection stems from the inability to produce multiple anti-microbial peptides, and transcriptional analyses suggest that the overexpression of Dgrn enhances the transcriptional output of the NF-ĸB related Toll and immune deficiency (IMD)-pathways. Moreover, expression of Dgrn alleviated the inhibitory impact of the cytoplasmic NF-ĸB inhibitor Cactus and the nuclear co-repressor Groucho/TLE (Gro). Additionally, we found that Dgrn is required for the local regenerative response of the mid-gut following infection. Upon oral infection, dgrn mutant flies fail to activate the Delta-Notch pathway in stem cells and enteroblasts, and are unable to regenerate and replace the damaged and dying enterocytes. Interestingly, the ubiquitin-specific protease CG8334 (dUSP32/dUSP11) antagonizes Dgrn activity in the gut, and halving the dose of CG8334 restores Delta-Notch signaling and rescues the lethality observed in dgrn mutants. Collectively, our data suggest that Dgrn is essential for both systemic and local tissue response to infection.
2015
Chamy, L El; Matt, N; Ntwasa, M; Reichhart, J M
The multilayered innate immune defense of the gut Journal Article
In: Biomed J, vol. 38, no. 4, pp. 276-284, 2015, ISBN: 26068126, (2320-2890 (Electronic) 2319-4170 (Linking) Journal Article Research Support, Non-U.S. Gov't Review).
@article{nokey,
title = {The multilayered innate immune defense of the gut},
author = {L El Chamy and N Matt and M Ntwasa and J M Reichhart},
url = {http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=26068126},
doi = {10.4103/2319-4170.158621},
isbn = {26068126},
year = {2015},
date = {2015-01-01},
journal = {Biomed J},
volume = {38},
number = {4},
pages = {276-284},
abstract = {In the wild, the fruit fly Drosophila melanogaster thrives on rotten fruit. The digestive tract maintains a powerful gut immune barrier to regulate the ingested microbiota, including entomopathogenic bacteria. This gut immune barrier includes a chitinous peritrophic matrix that isolates the gut contents from the epithelial cells. In addition, the epithelial cells are tightly sealed by septate junctions and can mount an inducible immune response. This local response can be activated by invasive bacteria, or triggered by commensal bacteria in the gut lumen. As with chronic inflammation in mammals, constitutive activation of the gut innate immune response is detrimental to the health of flies. Accordingly, the Drosophila gut innate immune response is tightly regulated to maintain the endogenous microbiota, while preventing infections by pathogenic microorganisms.},
note = {2320-2890 (Electronic)
2319-4170 (Linking)
Journal Article
Research Support, Non-U.S. Gov't
Review},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In the wild, the fruit fly Drosophila melanogaster thrives on rotten fruit. The digestive tract maintains a powerful gut immune barrier to regulate the ingested microbiota, including entomopathogenic bacteria. This gut immune barrier includes a chitinous peritrophic matrix that isolates the gut contents from the epithelial cells. In addition, the epithelial cells are tightly sealed by septate junctions and can mount an inducible immune response. This local response can be activated by invasive bacteria, or triggered by commensal bacteria in the gut lumen. As with chronic inflammation in mammals, constitutive activation of the gut innate immune response is detrimental to the health of flies. Accordingly, the Drosophila gut innate immune response is tightly regulated to maintain the endogenous microbiota, while preventing infections by pathogenic microorganisms.