Increasing evidence indicates that infection-triggered host defenses are regulated by the nervous system. However, the precise mechanisms of this regulation are not well understood. Here, we demonstrate that neuronal G protein-coupled receptor NPR-8 negatively regulates Caenorhabditis elegans defense against pathogen infection by suppressing cuticular collagen expression. NPR-8 controls the dynamics of cuticle structure in response to infection, likely through its regulation of cuticular collagen genes which, in turn, affects the nematode's defense. We further show that the defense activity of NPR-8 is confined to amphid sensory neurons AWB, ASJ, and AWC. It is generally believed that physical barrier defenses are not a response to infections but are part of the body's basic innate defense against pathogens. Our results challenge this view by showing not only that C. elegans cuticle structure dynamically changes in response to infection but also that the cuticle barrier defense is regulated by the nervous system.
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