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Nat Immunol. 2008 Oct;9(10):1165-70. doi: 10.1038/ni.1643. Epub 2008 Aug 24.

Sensing of 'danger signals' and pathogen-associated molecular patterns defines binary signaling pathways 'upstream' of Toll.

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Institut de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique Unité Propre de Recherche 9022, Université Louis Pasteur, Strasbourg Cedex, France.


In drosophila, molecular determinants from fungi and Gram-positive bacteria are detected by circulating pattern-recognition receptors. Published findings suggest that such pattern-recognition receptors activate as-yet-unidentified serine-protease cascades that culminate in the cleavage of Spätzle, the endogenous Toll receptor ligand, and trigger the immune response. We demonstrate here that the protease Grass defines a common activation cascade for the detection of fungi and Gram-positive bacteria mediated by pattern-recognition receptors. The serine protease Persephone, shown before to be specific for fungal detection in a cascade activated by secreted fungal proteases, was also required for the sensing of proteases elicited by bacteria in the hemolymph. Hence, Persephone defines a parallel proteolytic cascade activated by 'danger signals' such as abnormal proteolytic activities.

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