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Neuroendocrine signals modulate the innate immunity of Caenorhabditis elegans through insulin signaling

Nature Immunology volume 9, pages 1415–1424 (2008)Cite this article

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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Figure 1: Diminished secretion of neuropeptides from DCV confers greater resistance to killing by PA14.
Figure 2: Prolonged survival of neurosecretion mutants correlates with greater resistance to colonization by PA14 and higher expression of immunity-related genes.
Figure 3: Hypersecretion confers sensitivity to pathogens.
Figure 4: Neuroendocrine regulation of the antimicrobial response occurs through insulin signaling.
Figure 5: Neuronal function of ins-7 regulates immunity.

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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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  1. Department of Genetics, Department of Microbiology and Immunology, and Program in Immunology, Stanford University School of Medicine, Stanford, 94305, California, USA

    Trupti Kawli & Man-Wah Tan

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  1. Trupti Kawli
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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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Correspondence to Man-Wah Tan.

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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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