MALT-1 mediates IL-17 neural signaling to regulate C. elegans behavior, immunity and longevity

• Published in: Nature communications 2020-04, Vol.11 (1), p.2099-15, Article 2099
• Main Authors: Flynn, Sean M., Chen, Changchun, Artan, Murat, Barratt, Stephen, Crisp, Alastair, Nelson, Geoffrey M., Peak-Chew, Sew-Yeu, Begum, Farida, Skehel, Mark, de Bono, Mario
• Format: Article
• Language: English
• Subjects: 631/378/340; 631/378/371; 64/11; 82/58; 96; 96/21; 96/47; Animals; Associative learning; Behavior, Animal; Caenorhabditis elegans - drug effects; Caenorhabditis elegans - genetics; Caenorhabditis elegans - immunology; Caenorhabditis elegans - physiology; Caenorhabditis elegans Proteins - metabolism; Circuits; Cytokines; Escape behavior; Escape learning; Gene Expression Regulation - drug effects; Green Fluorescent Proteins - metabolism; Homology; Humanities and Social Sciences; Immunity; Immunity - drug effects; Immunoprecipitation; Inflammation; Interleukin 17; Interleukin-17 - metabolism; Interneurons - drug effects; Interneurons - physiology; Learning; Longevity; Longevity - drug effects; Mass spectrometry; Mass spectroscopy; Models, Biological; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein - metabolism; multidisciplinary; Nervous system; Neurons; Neurons - drug effects; Neurons - metabolism; Oxygen - pharmacology; Paracaspases; Phenotypes; Receptor mechanisms; Receptors; Science; Science (multidisciplinary); Signal Transduction - drug effects; Signaling; Subcellular Fractions - metabolism; Transgenes; Worms
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-15872-y

Besides pro-inflammatory roles, the ancient cytokine interleukin-17 (IL-17) modulates neural circuit function. We investigate IL-17 signaling in neurons, and the extent it can alter organismal phenotypes. We combine immunoprecipitation and mass spectrometry to biochemically characterize endogenous signaling complexes that function downstream of IL-17 receptors in C. elegans neurons. We identify the paracaspase MALT-1 as a critical output of the pathway. MALT1 mediates signaling from many immune receptors in mammals, but was not previously implicated in IL-17 signaling or nervous system function. C. elegans MALT-1 forms a complex with homologs of Act1 and IRAK and appears to function both as a scaffold and a protease. MALT-1 is expressed broadly in the C. elegans nervous system, and neuronal IL-17–MALT-1 signaling regulates multiple phenotypes, including escape behavior, associative learning, immunity and longevity. Our data suggest MALT1 has an ancient role modulating neural circuit function downstream of IL-17 to remodel physiology and behavior. IL-17 is a pro-inflammatory molecule that can also regulate neural circuit function. Here the authors use C. elegans to show that the paracaspase MALT-1 lies downstream of IL-17 signaling and regulates many aspects of C. elegans biology, including escape behavior, associative learning, immunity and longevity.