RRC ID 53315
Author Cao X, Aballay A.
Title Neural Inhibition of Dopaminergic Signaling Enhances Immunity in a Cell-Non-autonomous Manner.
Journal Curr Biol
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.
Volume 26(17)
Pages 2329-34
Published 2016-9-12
DOI 10.1016/j.cub.2016.06.036
PII S0960-9822(16)30675-3
PMID 27524480
PMC PMC5021569
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Chlorpromazine / pharmacology Dopamine / physiology* Dopamine Antagonists / pharmacology Immunity, Innate* Neural Inhibition Neurons / physiology Receptors, Dopamine D2 / genetics* Receptors, Dopamine D2 / metabolism Signal Transduction*
IF 9.601
Times Cited 21
C.elegans tm1392