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

Nature Immunology volume 9, pages 1165–1170 (2008)Cite this article

Abstract

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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Figure 1: Grass is involved in the sensing of both fungal infection and infection with Gram-positive bacteria.
Figure 2: Isolation of the SPE mutation Pasteur.
Figure 3: Grass acts 'downstream' of PRRs.
Figure 4: Grass and Psh define two parallel pathways that cooperatively activate Toll.
Figure 5: Psh is activated by bacterial proteolytic activities in the hemolymph.

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Acknowledgements

We dedicate this work to the memory of A. Killinc, who found the original Pasteur mutation. We thank L. Gutmann (Institut National de la Santé et de la Recherche Médicale U872) for E. faecalis peptidoglycan and A. Meunier, S. Ozkan and R. Walther for technical help. Supported by the French Research Ministry (L.E.C.), Association pour la Recherche contre le Cancer (L.E.C.), Centre National de la Recherche Scientifique and the National Institutes of Health (5PO1-AI044220-09).

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  1. Laure El Chamy and Vincent Leclerc: These authors contributed equally to this work.

Authors and Affiliations

  1. Institut de Biologie Moléculaire et Cellulaire, Centre National de la Recherche Scientifique Unité Propre de Recherche 9022, Université Louis Pasteur, Strasbourg, 67084, Cedex, France

    Laure El Chamy, Vincent Leclerc, Isabelle Caldelari & Jean-Marc Reichhart

Authors
  1. Laure El Chamy
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  2. Vincent Leclerc
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  4. Jean-Marc Reichhart
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Contributions

L.E.C. and V.L. designed and did most of the experiments; I.C. contributed to the experiments and to manuscript criticism; and J.-M.R. directed the experiments and wrote the paper with L.E.C. and V.L.

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Correspondence to Jean-Marc Reichhart.

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Chamy, L., Leclerc, V., Caldelari, I. et al. Sensing of 'danger signals' and pathogen-associated molecular patterns defines binary signaling pathways 'upstream' of Toll. Nat Immunol 9, 1165–1170 (2008). https://doi.org/10.1038/ni.1643

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