Open Close
Ragab, A., Buechling, T., Gesellchen, V., Spirohn, K., Boettcher, A.L., Boutros, M. (2011). Drosophila Ras/MAPK signalling regulates innate immune responses in immune and intestinal stem cells.  EMBO J. 30(6): 1123--1136.
FlyBase ID
Publication Type
Research paper

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.

PubMed ID
PubMed Central ID
PMC3061042 (PMC) (EuropePMC)
Related Publication(s)

Negative regulation of immune responses on the fly.
Lee and Ferrandon, 2011, EMBO J. 30(6): 988--990 [FBrf0214407]

Associated Information
Associated Files
Other Information
Secondary IDs
    Language of Publication
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    EMBO J.
    The EMBO Journal
    Publication Year
    Data From Reference