title: Neural Inhibition of Dopaminergic Signaling Enhances Immunity in a Cell-Non-autonomous Manner.
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.
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Xiou
authors.initials: X
authors.lastname: Cao
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA. Electronic address: a.aballay@duke.edu.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Aballay
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002746:Chlorpromazine / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D007113:Immunity, Innate; D009433:Neural Inhibition; D009474:Neurons / Q000502:physiology; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; C503952:DOP-4 protein, C elegans; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D002746:Chlorpromazine; D004298:Dopamine