The Jak-STAT signaling pathway is required but not sufficient for the antiviral response of drosophila

Catherine Dostert; Emmanuelle Jouanguy; Phil Irving; Laurent Troxler; Delphine Galiana-Arnoux; Charles Hetru; Jules A. Hoffmann; Jean Luc Imler

doi:10.1038/ni1237

The Jak-STAT signaling pathway is required but not sufficient for the antiviral response of drosophila

Catherine Dostert, Emmanuelle Jouanguy, Phil Irving, Laurent Troxler, Delphine Galiana-Arnoux, Charles Hetru, Jules A. Hoffmann, Jean Luc Imler^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

525 Citations (Scopus)

Abstract

The response of drosophila to bacterial and fungal infections involves two signaling pathways, Toll and Imd, which both activate members of the transcription factor NF-κB family. Here we have studied the global transcriptional response of flies to infection with drosophila C virus. Viral infection induced a set of genes distinct from those regulated by the Toll or Imd pathways and triggered a signal transducer and activator of transcription (STAT) DNA-binding activity. Genetic experiments showed that the Jak kinase Hopscotch was involved in the control of the viral load in infected flies and was required but not sufficient for the induction of some virus-regulated genes. Our results indicate that in addition to Toll and Imd, a third, evolutionary conserved innate immunity pathway functions in drosophila and counters viral infection.

Original language	English
Pages (from-to)	946-953
Number of pages	8
Journal	Nature Immunology
Volume	6
Issue number	9
DOIs	https://doi.org/10.1038/ni1237
Publication status	Published - Sept 2005
Externally published	Yes

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title = "The Jak-STAT signaling pathway is required but not sufficient for the antiviral response of drosophila",

abstract = "The response of drosophila to bacterial and fungal infections involves two signaling pathways, Toll and Imd, which both activate members of the transcription factor NF-κB family. Here we have studied the global transcriptional response of flies to infection with drosophila C virus. Viral infection induced a set of genes distinct from those regulated by the Toll or Imd pathways and triggered a signal transducer and activator of transcription (STAT) DNA-binding activity. Genetic experiments showed that the Jak kinase Hopscotch was involved in the control of the viral load in infected flies and was required but not sufficient for the induction of some virus-regulated genes. Our results indicate that in addition to Toll and Imd, a third, evolutionary conserved innate immunity pathway functions in drosophila and counters viral infection.",

author = "Catherine Dostert and Emmanuelle Jouanguy and Phil Irving and Laurent Troxler and Delphine Galiana-Arnoux and Charles Hetru and Hoffmann, {Jules A.} and Imler, {Jean Luc}",

note = "Funding Information: We thank S. Ozkan for help with transgenesis; M.-C. Lacombe for assistance with real-time quantitative RT-PCR analysis; J. Mutterer and D. Zachary for help with the confocal microscopy; E. Santiago for technical support; D. Ferrandon and J. Royet for discussions and critical reading of the manuscript; N. Perrimon, J. Castelli-Gair Hombria and J. Darnell for providing fly stocks; and A. Schneemann for the FHV stock and discussions. Supported by Centre National de la Recherche Scientifique and Minist{\`e}re de la Recherche et de la Technologie (Actions Concert{\'e}es Incitatives Physiologie Int{\'e}grative and Microbiologie, and Programme puces Affymetrix); Institut Universitaire de France; Ligue contre le Cancer (E.J.); Centre National de la Recherche Scientifique (D.G.A.); and Minist{\`e}re de la Recherche du Grand-Duch{\'e} de Luxembourg (C.D.).",

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AU - Galiana-Arnoux, Delphine

AU - Hetru, Charles

AU - Hoffmann, Jules A.

AU - Imler, Jean Luc

N1 - Funding Information: We thank S. Ozkan for help with transgenesis; M.-C. Lacombe for assistance with real-time quantitative RT-PCR analysis; J. Mutterer and D. Zachary for help with the confocal microscopy; E. Santiago for technical support; D. Ferrandon and J. Royet for discussions and critical reading of the manuscript; N. Perrimon, J. Castelli-Gair Hombria and J. Darnell for providing fly stocks; and A. Schneemann for the FHV stock and discussions. Supported by Centre National de la Recherche Scientifique and Ministère de la Recherche et de la Technologie (Actions Concertées Incitatives Physiologie Intégrative and Microbiologie, and Programme puces Affymetrix); Institut Universitaire de France; Ligue contre le Cancer (E.J.); Centre National de la Recherche Scientifique (D.G.A.); and Ministère de la Recherche du Grand-Duché de Luxembourg (C.D.).

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N2 - The response of drosophila to bacterial and fungal infections involves two signaling pathways, Toll and Imd, which both activate members of the transcription factor NF-κB family. Here we have studied the global transcriptional response of flies to infection with drosophila C virus. Viral infection induced a set of genes distinct from those regulated by the Toll or Imd pathways and triggered a signal transducer and activator of transcription (STAT) DNA-binding activity. Genetic experiments showed that the Jak kinase Hopscotch was involved in the control of the viral load in infected flies and was required but not sufficient for the induction of some virus-regulated genes. Our results indicate that in addition to Toll and Imd, a third, evolutionary conserved innate immunity pathway functions in drosophila and counters viral infection.

AB - The response of drosophila to bacterial and fungal infections involves two signaling pathways, Toll and Imd, which both activate members of the transcription factor NF-κB family. Here we have studied the global transcriptional response of flies to infection with drosophila C virus. Viral infection induced a set of genes distinct from those regulated by the Toll or Imd pathways and triggered a signal transducer and activator of transcription (STAT) DNA-binding activity. Genetic experiments showed that the Jak kinase Hopscotch was involved in the control of the viral load in infected flies and was required but not sufficient for the induction of some virus-regulated genes. Our results indicate that in addition to Toll and Imd, a third, evolutionary conserved innate immunity pathway functions in drosophila and counters viral infection.

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The Jak-STAT signaling pathway is required but not sufficient for the antiviral response of drosophila

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