Drosophila Ras/MAPK signalling regulates innate immune responses in immune and intestinal stem cells

Ragab A, Buechling T, Gesellchen V, Spirohn. K, Boettcher A. L. and Boutros M. 2011. EMBO. 30, 1123–1136

Speaker: Chun-Ru Lin (林純如)                                   Time: 14:00~15:00, Nov. 9, 2011

Commentator: Dr. Jhih-Wei Shin (辛致煒老師)          Place: Room 601

Abstract:

Drosophila is a potent model for the study of innate immune responses. Drosophila lacks adaptive immune responses, and relies mainly on two nuclear factor kappa-B (NF-kB) signaling pathways, commonly referred to as Toll and immune deficiency(IMD) pathways(1). These pathways regulate the production of antimicrobial peptides to defend the attacks by microorganisms. IMD signaling is mainly activated by Gram-negative bacteria, while Toll pathways are activated by Gram-positive bacteria. Recently, several large-scale RNAi screens were conducted to reveal novel regulators of the Drosophila IMD pathway. The authors utilized an global RNAi system to screen the negative regulators of IMD signaling in cultured Drosophila cells of haematopoetic origin, and several components of the Ras/MAPK signaling pathway, such as Ras85D, Sos and Dsor1, were revealed (2). The authors further confirmed that these components of the Ras/MAPK signaling pathway negatively regulate IMD signaling. They also demonstrated that knockdown of the positive regulators of the Ras/ MAPK pathway enhanced IMD signaling. Conversely, activation of the ectopic Ras/MAPK pathway results in the suppression of Drosophila IMD signaling. Moreover, the Ras pathway represses IMD signaling regardless with or without immune challenge. The authors further revealed that the Ras/MAPK pathway activates the IMD signaling through the negative regulator Pirk, a cytoplasmic protein interacting with IMD. All together, the authors clarified the role of Ras/MAPK pathway in modulating IMD signaling in adult Drosophila immune tissues, haemocytes, fat body and adult intestinal stem cells. In conclusion, this study reveals the novel components of the Ras/MAPK pathway which suppresses IMD pathway activity by Pirk. It provides an example of a pathway that mediates cell proliferation and regulates immune response.

References:

1. Ferrandon D, Imler J. L., Hetru C and Hoffmann J. A. 2007.The Drosophila systemic immune response: sensing and signaling during bacterial and fungal infections. Nat. Immunol. 7: 862–874.

2. Gesellchen V, Kuttenkeuler D, Steckel M, Pelte N and Boutros M. 2005. An RNA interference screen identifies inhibitor of apoptosis protein2 as a regulator of innate immune signaling in Drosophila. EMBO Rep 6: 979–984.