Ubiquitin signalling in Drosophila innate immune responses

• Published in: The FEBS journal Vol. 291; no. 20; pp. 4397 - 4413
• Main Authors: Aalto, Anna L., Luukkonen, Veera, Meinander, Annika
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.10.2024
• Subjects: Animals; Antimicrobial peptides; Apoptosis; Bacterial diseases; Cell activation; Cell proliferation; Cell survival; Chronic infection; deubiquitinating enzyme; Drosophila; Drosophila melanogaster - genetics; Drosophila melanogaster - immunology; Drosophila Proteins - genetics; Drosophila Proteins - immunology; Drosophila Proteins - metabolism; E3 ubiquitin ligase; Effector cells; Eiger; Fruit flies; Gene expression; Homeostasis; Humoral immunity; Imd pathway; Immune response; Immune response (humoral); Immune system; Immunity (Disease); Immunity, Innate - genetics; Innate immunity; Insects; JNK pathway; Lysosomes; Molecular modelling; NF‐κB; Pathogens; Peptides; Proteasomes; Proteins; Signal transduction; Signal Transduction - immunology; Toll pathway; Toll-Like Receptors - genetics; Toll-Like Receptors - immunology; Toll-Like Receptors - metabolism; Transcription activation; Transcription factors; Ubiquitin; Ubiquitin - genetics; Ubiquitin - immunology; Ubiquitin - metabolism; Ubiquitination; JNK pathway; Toll pathway; NF‐κB; innate immunity; deubiquitinating enzyme; ubiquitination; Drosophila; E3 ubiquitin ligase; Imd pathway; Eiger
• ISSN: 1742-464X; 1742-4658; 1742-4658
• DOI: 10.1111/febs.17028

Cells respond to invading pathogens and danger signals from the environment by adapting gene expression to meet the need for protective effector molecules. While this innate immune response is required for the cell and the organism to recover, excess immune activation may lead to loss of homeostasis, thereby promoting chronic inflammation and cancer progression. The molecular basis of innate immune defence is comprised of factors promoting survival and proliferation, such as cytokines, antimicrobial peptides and anti‐apoptotic proteins. As the molecular mechanisms regulating innate immune responses are conserved through evolution, the fruit fly Drosophila melanogaster serves as a convenient, affordable and ethical model organism to enhance understanding of immune signalling. Fly immunity against bacterial infection is built up by both cellular and humoral responses, where the latter is regulated by the Imd and Toll pathways activating NF‐κB transcription factors Relish, Dorsal and Dif, as well as JNK activation and JAK/STAT signalling. As in mammals, the Drosophila innate immune signalling pathways are characterised by ubiquitination of signalling molecules followed by ubiquitin receptors binding to the ubiquitin chains, as well as by rapid changes in protein levels by ubiquitin‐mediated targeted proteasomal and lysosomal degradation. In this review, we summarise the molecular signalling pathways regulating immune responses to pathogen infection in Drosophila, with a focus on ubiquitin‐dependent control of innate immunity and inflammatory signalling. Drosophila innate immunity against bacterial infection relies on humoral responses regulated by the Imd and Toll pathways activating NF‐κB transcription factors, as well as JNK activation and JAK/STAT signalling. These pathways are characterised by E3 ligases and deubiquitinating enzymes that determine ubiquitination of signalling molecules followed by ubiquitin receptors binding to the ubiquitin chains, and through rapid changes in protein levels facilitated by ubiquitin‐mediated targeted proteasomal degradation.