Imd pathway

Simplified diagram of Imd signalling as found in the fruit fly.

The Imd pathway is a broadly-conserved NF-κB immune signalling pathway of insects and some arthropods[1] that regulates a potent antibacterial defence response. The pathway is named after the discovery of a mutation causing severe immune deficiency (the gene was named "Imd" for "immune deficiency"). The Imd pathway was first discovered in 1995 using Drosophila fruit flies by Bruno Lemaitre and colleagues, who also later discovered that the Drosophila Toll gene regulated defence against Gram-positive bacteria and fungi.[2][3] Together the Toll and Imd pathways have formed a paradigm of insect immune signalling; as of September 2, 2019, these two landmark discovery papers have been cited collectively over 5000 times since publication on Google Scholar.[4][5]

The Imd pathway responds to signals produced by Gram-negative bacteria. Peptidoglycan recognition proteins (PGRPs) sense DAP-type peptidoglycan, which activates the Imd signalling cascade. This culminates in the translocation of the NF-κB transcription factor Relish, leading to production of antimicrobial peptides and other effectors.[6] Insects lacking Imd signalling either naturally or by genetic manipulation are extremely susceptible to infection by a wide variety of pathogens and especially bacteria.

  1. ^ Palmer WJ, Jiggins FM (August 2015). "Comparative Genomics Reveals the Origins and Diversity of Arthropod Immune Systems". Molecular Biology and Evolution. 32 (8): 2111–2129. doi:10.1093/molbev/msv093. PMC 4833078. PMID 25908671.
  2. ^ Lemaitre B, Kromer-Metzger E, Michaut L, Nicolas E, Meister M, Georgel P, et al. (October 1995). "A recessive mutation, immune deficiency (imd), defines two distinct control pathways in the Drosophila host defense". Proceedings of the National Academy of Sciences of the United States of America. 92 (21): 9465–9469. Bibcode:1995PNAS...92.9465L. doi:10.1073/pnas.92.21.9465. PMC 40822. PMID 7568155.
  3. ^ Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA (September 1996). "The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults". Cell. 86 (6): 973–983. doi:10.1016/s0092-8674(00)80172-5. PMID 8808632. S2CID 10736743.
  4. ^ "A recessive mutation, immune deficiency (imd), defines two distinct control pathways in the Drosophila host defense". Google Scholar. Retrieved 2 September 2019.
  5. ^ "The dorsoventral regulatory gene cassette spätzle/Toll/cactus controls the potent antifungal response in Drosophila adults". Google Scholar. Retrieved 2 September 2019.
  6. ^ Lemaitre B, Hoffmann J (2007). "The host defense of Drosophila melanogaster". Annual Review of Immunology. 25: 697–743. doi:10.1146/annurev.immunol.25.022106.141615. PMID 17201680.