Journal
EMBO JOURNAL
Volume 30, Issue 6, Pages 1123-1136Publisher
WILEY
DOI: 10.1038/emboj.2011.4
Keywords
Drosophila; innate immunity; intestinal stem cells; MAPK; RNAi
Categories
Funding
- DKFZ
- Helmholtz Alliance for Systems Biology, FP7 CancerPathways
- Deutsche Forschungsgemeinschaft
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Immune signalling pathways need to be tightly regulated as overactivation of these pathways can result in chronic inflammatory diseases and cancer. NF-kappa B 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-kappa B 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-kappa B 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. The EMBO Journal (2011) 30, 1123-1136. doi:10.1038/emboj.2011.4; Published online 4 February 2011
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