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Mol Cell. 2018 Feb 15;69(4):539-550.e6. doi: 10.1016/j.molcel.2018.01.029.

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

Author information

1
Université de Strasbourg, CNRS, Modèles Insectes d'Immunité Innée, UPR9022, F-67000 Strasbourg, France.
2
Laboratoire de Spectrométrie de Masse Bio-Organique, Université de Strasbourg, CNRS, IPHC, UMR 7178, F-67000 Strasbourg, France.
3
Université de Strasbourg, CNRS, Modèles Insectes d'Immunité Innée, UPR9022, F-67000 Strasbourg, France. Electronic address: f.veillard@ibmc-cnrs.unistra.fr.

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.

KEYWORDS:

NF-κB pathway; bacterial proteases; cathepsin 26-29-p; clip-serine protease; cysteine cathepsin; danger signal; fungal proteases; immune receptor; innate immunity; virulence factors

PMID:
29452635
PMCID:
PMC5823974
DOI:
10.1016/j.molcel.2018.01.029
[Indexed for MEDLINE]
Free PMC Article

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