A serpin mutant links Toll activation to melanization in the host defence of Drosophila

A prominent response during the Drosophila host defence is the induction of proteolytic cascades, some of which lead to localized melanization of pathogen surfaces, while others activate one of the major players in the systemic antimicrobial response, the Toll pathway. Despite the fact that gain‐of‐function mutations in the Toll receptor gene result in melanization, a clear link between Toll activation and the melanization reaction has not been firmly established. Here, we present evidence for the coordination of hemolymph‐borne melanization with activation of the Toll pathway in the Drosophila host defence. The melanization reaction requires Toll pathway activation and depends on the removal of the Drosophila serine protease inhibitor Serpin27A. Flies deficient for this serpin exhibit spontaneous melanization in larvae and adults. Microbial challenge induces its removal from the hemolymph through Toll‐dependent transcription of an acute phase immune reaction component.

[1]  B. Lemaître,et al.  An immune-responsive Serpin regulates the melanization cascade in Drosophila. , 2002, Developmental cell.

[2]  J. Hoffmann,et al.  Activation of Drosophila Toll During Fungal Infection by a Blood Serine Protease , 2002, Science.

[3]  T. Sommer,et al.  BiP binding keeps ATF6 at bay. , 2002, Developmental cell.

[4]  G. Rubin,et al.  The Toll and Imd pathways are the major regulators of the immune response in Drosophila , 2002, The EMBO journal.

[5]  D. Ferrandon,et al.  Cutting Edge: The Toll Pathway Is Required for Resistance to Gram-Positive Bacterial Infections in Drosophila1 , 2002, The Journal of Immunology.

[6]  J. Hoffmann,et al.  Drosophila innate immunity: an evolutionary perspective , 2002, Nature Immunology.

[7]  M. Belvin,et al.  A genome-wide analysis of immune responses in Drosophila , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[8]  Paul T. Spellman,et al.  Genome-wide analysis of the Drosophila immune response by using oligonucleotide microarrays , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[9]  J. Whisstock,et al.  The Serpins Are an Expanding Superfamily of Structurally Similar but Functionally Diverse Proteins , 2001, The Journal of Biological Chemistry.

[10]  A M Lesk,et al.  Phylogeny of the serpin superfamily: implications of patterns of amino acid conservation for structure and function. , 2000, Genome research.

[11]  R. Zhou,et al.  Role of Drosophila IKKγ in a Toll-independent antibacterial immune response , 2000, Nature Immunology.

[12]  M. Kim,et al.  A masquerade-like serine proteinase homologue is necessary for phenoloxidase activity in the coleopteran insect, Holotrichia diomphalia larvae. , 2000, European journal of biochemistry.

[13]  J. Hoffmann,et al.  The Rel protein DIF mediates the antifungal but not the antibacterial host defense in Drosophila. , 2000, Immunity.

[14]  Doo-Sang Park,et al.  Immunological Detection of Serpin in the Fall Webworm, Hyphantria cunea and Its Inhibitory Activity on the Prophenoloxidase System , 2000, Molecules and cells.

[15]  Haobo Jiang,et al.  The clip-domain family of serine proteinases in arthropods. , 2000, Insect biochemistry and molecular biology.

[16]  L. Stevens,et al.  Spatially Restricted Expression of pipe in the Drosophila Egg Chamber Defines Embryonic Dorsal–Ventral Polarity , 1998, Cell.

[17]  Haobo Jiang,et al.  Pro-phenol oxidase activating proteinase from an insect, Manduca sexta: a bacteria-inducible protein similar to Drosophila easter. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[18]  S. Govind,et al.  A role for the Drosophila Toll/Cactus pathway in larval hematopoiesis. , 1998, Development.

[19]  L. Cerenius,et al.  Role of the prophenoloxidase-activating system in invertebrate immunity. , 1998, Current opinion in immunology.

[20]  D. Hultmark,et al.  Molecular mechanisms of immune responses in insects. , 1998 .

[21]  Haobo Jiang,et al.  Characterization and Functional Analysis of 12 Naturally Occurring Reactive Site Variants of Serpin-1 from Manduca sexta* , 1997, The Journal of Biological Chemistry.

[22]  N. Chosa,et al.  Activation of prophenoloxidase A1 by an activating enzyme in Drosophila melanogaster. , 1997, Insect biochemistry and molecular biology.

[23]  M. Ashida Recent advances in research on the insect prophenoloxidase cascade , 1997 .

[24]  B. Lemaître,et al.  The Dorsoventral Regulatory Gene Cassette spätzle/Toll/cactus Controls the Potent Antifungal Response in Drosophila Adults , 1996, Cell.

[25]  S. Govind Rel signalling pathway and the melanotic tumour phenotype of Drosophila. , 1996, Biochemical Society transactions.

[26]  A. Nappi,et al.  Superoxide anion generation in Drosophila during melanotic encapsulation of parasites. , 1995, European journal of cell biology.

[27]  P. Brey,et al.  Role of the integument in insect defense: pro-phenol oxidase cascade in the cuticular matrix. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[28]  R. Steward,et al.  Functional analysis and regulation of nuclear import of dorsal during the immune response in Drosophila. , 1995, The EMBO journal.

[29]  Takuji Sasaki,et al.  A target protease activity of serpins in insect hemolymph , 1994 .

[30]  A. Nappi,et al.  Melanogenesis and the generation of cytotoxic molecules during insect cellular immune reactions. , 1993, Pigment cell research.

[31]  N. Perrimon,et al.  Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. , 1993, Development.

[32]  K. Anderson,et al.  Zygotic expression and activity of the Drosophila Toll gene, a gene required maternally for embryonic dorsal-ventral pattern formation. , 1988, Genetics.

[33]  A. Pye Microbial activation of prophenoloxidase from immune insect larvae , 1974, Nature.