Abstract
Communication between the immune and nervous systems, each of which is able to react rapidly to environmental stimuli, may confer a survival advantage. However, precisely how the nervous system influences the immune response and whether neural modulation of immune function is biologically important are not well understood. Here we report that neuronal exocytosis of neuropeptides from dense core vesicles suppressed the survival of Caenorhabditis elegans and their clearance of infection with the human bacterial pathogen Pseudomonas aeruginosa. This immunomodulatory function was mediated by INS-7, an insulin-like neuropeptide whose induction was associated with Pseudomonas virulence. INS-7 secreted from the nervous system functioned in a non–cell autonomous way to activate the insulin pathway and alter basal and inducible expression of immunity-related genes in intestinal cells.
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Acknowledgements
We thank W. Chen and E. Evans for strain construction (ins-7(lf) 'rescue' under Pins-7 and Punc-119); A. Fire (Stanford University) for advice, vectors and use of the microinjection apparatus; S. Cohen for microscope use; K. Miller (Oklahoma Medical Research Foundation), K. Strange (Vanderbilt University), C. Darby (University of California, San Francisco), C. Kenyon (University of California, San Francisco), and K. Shen (Stanford University) for sharing strains and vectors; and all members of the Tan laboratory, A. Brunet and V. Nanjundiah for critical review and discussion of this work. Some nematode strains were provided by the Caenorhabditis Genetics Center (funded by the US National Institutes of Health National Center for Research Resources); the ins-7 mutant was provided by the Japanese National BioResource Project (funded by the Ministry of Education, Culture, Science, Sports and Technology, Japan). Supported by the US National Institutes of Health (GM66269 to M.-W.T.).
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T.K. did the experiments, and T.K. and M.-W.T. designed the experiments and wrote the paper.
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Kawli, T., Tan, MW. Neuroendocrine signals modulate the innate immunity of Caenorhabditis elegans through insulin signaling. Nat Immunol 9, 1415–1424 (2008). https://doi.org/10.1038/ni.1672
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DOI: https://doi.org/10.1038/ni.1672
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