Neural Inhibition of Dopaminergic Signaling Enhances Immunity in a Cell-Non-autonomous Manner

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2329-2334
Number of pages6
JournalCurrent Biology
Volume26
Issue number17
DOIs
StatePublished - Sep 12 2016
Externally publishedYes

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Neural Inhibition
Neurology
nervous system
Nervous System
Immunity
immunity
dopamine
Neurons
Dopamine
neurons
chlorpromazine
Dopamine D1 Receptors
Immune system
Chlorpromazine
Dopamine Receptors
Caenorhabditis elegans
p38 Mitogen-Activated Protein Kinases
cells
bacterial infections
mitogen-activated protein kinase

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Neural Inhibition of Dopaminergic Signaling Enhances Immunity in a Cell-Non-autonomous Manner. / Cao, Xiou; Aballay, Alejandro.

In: Current Biology, Vol. 26, No. 17, 12.09.2016, p. 2329-2334.

Research output: Contribution to journalArticle

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