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

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Drosophila / immunology*
  • Drosophila / microbiology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / immunology*
  • Drosophila Proteins / metabolism
  • Fungi / immunology
  • Gram-Positive Bacteria / immunology
  • Gram-Positive Bacterial Infections / immunology
  • In Situ Hybridization
  • Mycoses / immunology
  • Peptide Hydrolases / immunology
  • Peptide Hydrolases / metabolism
  • 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


  • Drosophila Proteins
  • Receptors, Pattern Recognition
  • Toll-Like Receptors
  • spz protein, Drosophila
  • Peptide Hydrolases
  • Serine Endopeptidases
  • psh protein, Drosophila