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Abstract
The innate immune system is the front line of host defense against microbial infections,
but its rapid and uncontrolled activation elicits microbicidal mechanisms that have
deleterious effects [1, 2]. Increasing evidence indicates that the metazoan nervous
system, which responds to stimuli originating from both the internal and the external
environment, functions as a modulatory apparatus that controls not only microbial
killing pathways but also cellular homeostatic mechanisms [3-5]. Here we report that dopamine
signaling controls innate immune responses through a D1-like dopamine receptor, DOP-4,
in Caenorhabditis elegans. Chlorpromazine inhibition of DOP-4 in the nervous system
activates a microbicidal PMK-1/p38 mitogen-activated protein kinase signaling pathway
that enhances host resistance against bacterial infections. The immune inhibitory
function of dopamine originates in CEP neurons and requires active DOP-4 in downstream
ASG neurons. Our findings indicate that dopamine signaling from the nervous system
controls immunity in a cell-non-autonomous manner and identifies the dopaminergic
system as a potential therapeutic target for not only infectious diseases but also
a range of conditions that arise as a consequence of malfunctioning immune responses.