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

• Published in: Nature immunology Vol. 9; no. 10; pp. 1165 - 1170
• Main Authors: Reichhart, Jean-Marc, Leclerc, Vincent, Caldelari, Isabelle, Chamy, Laure El
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.10.2008; Nature Publishing Group
• Subjects: Animals; Animals, Genetically Modified; Bacteria; Biomedical and Life Sciences; Biomedicine; Cell receptors; Cellular signal transduction; Drosophila; Drosophila - immunology; Drosophila - microbiology; Drosophila Proteins - genetics; Drosophila Proteins - immunology; Drosophila Proteins - metabolism; Fungi - immunology; Gram-Positive Bacteria - immunology; Gram-Positive Bacterial Infections - immunology; Grasses; Health aspects; Immune response; Immunology; In Situ Hybridization; Infectious Diseases; Mycoses - immunology; Peptide Hydrolases - immunology; Peptide Hydrolases - metabolism; Physiological aspects; Receptors, Pattern Recognition - immunology; Receptors, Pattern Recognition - metabolism; Serine Endopeptidases - genetics; Serine Endopeptidases - immunology; Serine Endopeptidases - metabolism; Signal Transduction - immunology; Toll-Like Receptors - immunology; Toll-Like Receptors - metabolism; France
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni.1643

Microbial sensors activate the Toll pathway in flies. Reichhart and colleagues identify the serine protease Grass, which acts in parallel with Persephone to cleave Toll-activating Spatzle in response to Gram-positive bacteria and fungi. 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.