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Drosophila Ras/MAPK signalling regulates innate immune responses in immune and intestinal stem cells.
Ragab, Anan; Buechling, Tina; Gesellchen, Viola; Spirohn, Kerstin; Boettcher, Anna-Lisa; Boutros, Michael.
Afiliación
  • Ragab A; German Cancer Research Center (DKFZ), Division of Signaling and Functional Genomics, Department of Cell and Molecular Biology, University of Heidelberg, Faculty of Medicine Mannheim, Heidelberg, Germany.
EMBO J ; 30(6): 1123-36, 2011 Mar 16.
Article en En | MEDLINE | ID: mdl-21297578
Immune signalling pathways need to be tightly regulated as overactivation of these pathways can result in chronic inflammatory diseases and cancer. NF-κB signalling and associated innate immune pathways are crucial in the first line of defense against infection in all animals. In a genome-wide RNAi screen for modulators of Drosophila immune deficiency (IMD)/NF-κB signalling, we identified components of the Ras/MAPK pathway as essential for suppression of IMD pathway activity, even in the absence of an immune challenge. Downregulation of Ras/MAPK activity mimics the induction of innate immune responses by microbial patterns. Conversely, ectopic Ras/MAPK pathway activation results in the suppression of Drosophila IMD/NF-κB signalling. Mechanistically, we show that the Ras/MAPK pathway acts by inducing transcription of the IMD pathway inhibitor Pirk/Rudra/PIMS. Finally, in vivo experiments demonstrate a requirement for Ras/MAPK signalling in restricting innate immune responses in haemocytes, fat body and adult intestinal stem cells. Our observations provide an example of a pathway that promotes cell proliferation and has simultaneously been utilized to limit the immune response.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: FN-kappa B / Proteínas ras / Proteínas Quinasas Activadas por Mitógenos / Proteínas de Drosophila / Drosophila melanogaster / Inmunidad Innata Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: EMBO J Año: 2011 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: FN-kappa B / Proteínas ras / Proteínas Quinasas Activadas por Mitógenos / Proteínas de Drosophila / Drosophila melanogaster / Inmunidad Innata Tipo de estudio: Prognostic_studies Límite: Animals Idioma: En Revista: EMBO J Año: 2011 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido