Octopaminergic Signaling Mediates Neural Regulation of Innate Immunity in <named-content content-type="genus-species">Caenorhabditis elegans</named-content>

ABSTRACT Upon pathogen infection, the nervous system regulates innate immunity to confer coordinated protection to the host. However, the precise mechanisms of such regulation remain unclear. Previous studies have demonstrated that OCTR-1, a putative G protein-coupled receptor for catecholamine, fun...

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Autores principales:	Durai Sellegounder, Chung-Hsiang Yuan, Phillip Wibisono, Yiyong Liu, Jingru Sun
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Caenorhabditis elegans G protein-coupled receptor innate immunity neural regulation octopamine Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/8aee613a45094d15884ab324fbc9c51d
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spelling	oai:doaj.org-article:8aee613a45094d15884ab324fbc9c51d2021-11-15T15:58:20ZOctopaminergic Signaling Mediates Neural Regulation of Innate Immunity in <named-content content-type="genus-species">Caenorhabditis elegans</named-content>10.1128/mBio.01645-182150-7511https://doaj.org/article/8aee613a45094d15884ab324fbc9c51d2018-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01645-18https://doaj.org/toc/2150-7511ABSTRACT Upon pathogen infection, the nervous system regulates innate immunity to confer coordinated protection to the host. However, the precise mechanisms of such regulation remain unclear. Previous studies have demonstrated that OCTR-1, a putative G protein-coupled receptor for catecholamine, functions in the sensory neurons designated “ASH” to suppress innate immune responses in Caenorhabditis elegans. It is unknown what molecules act as OCTR-1 ligands in the neural immune regulatory circuit. Here we identify neurotransmitter octopamine (OA) as an endogenous ligand for OCTR-1 in immune regulation and show that the OA-producing RIC neurons function in the OCTR-1 neural circuit to suppress innate immunity. RIC neurons are deactivated in the presence of pathogens but transiently activated by nonpathogenic bacteria. Our data support a model whereby an octopaminergic immunoinhibitory pathway is tonically active under normal conditions to maintain immunological homeostasis or suppress unwanted innate immune responses but downregulated upon pathogen infection to allow enhanced innate immunity. As excessive innate immune responses have been linked to a myriad of human health concerns, our study could potentially benefit the development of more-effective treatments for innate immune disorders. IMPORTANCE Insufficient or excessive immune responses to pathogen infection are major causes of disease. Increasing evidence indicates that the nervous system regulates the immune system to help maintain immunological homeostasis. However, the precise mechanisms of this regulation are largely unknown. Here we show the existence of an octopaminergic immunoinhibitory pathway in Caenorhabditis elegans. Our study results indicate that this pathway is tonically active under normal conditions to maintain immunological homeostasis or suppress unwanted innate immune responses but downregulated upon pathogen infection to allow enhanced innate immunity. As excessive innate immune responses have been linked to human health conditions such as Crohn's disease, rheumatoid arthritis, atherosclerosis, diabetes, and Alzheimer's disease, elucidating octopaminergic neural regulation of innate immunity could be helpful in the development of new treatments for innate immune diseases.Durai SellegounderChung-Hsiang YuanPhillip WibisonoYiyong LiuJingru SunAmerican Society for MicrobiologyarticleCaenorhabditis elegansG protein-coupled receptorinnate immunityneural regulationoctopamineMicrobiologyQR1-502ENmBio, Vol 9, Iss 5 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Caenorhabditis elegans G protein-coupled receptor innate immunity neural regulation octopamine Microbiology QR1-502
spellingShingle	Caenorhabditis elegans G protein-coupled receptor innate immunity neural regulation octopamine Microbiology QR1-502 Durai Sellegounder Chung-Hsiang Yuan Phillip Wibisono Yiyong Liu Jingru Sun Octopaminergic Signaling Mediates Neural Regulation of Innate Immunity in <named-content content-type="genus-species">Caenorhabditis elegans</named-content>
description	ABSTRACT Upon pathogen infection, the nervous system regulates innate immunity to confer coordinated protection to the host. However, the precise mechanisms of such regulation remain unclear. Previous studies have demonstrated that OCTR-1, a putative G protein-coupled receptor for catecholamine, functions in the sensory neurons designated “ASH” to suppress innate immune responses in Caenorhabditis elegans. It is unknown what molecules act as OCTR-1 ligands in the neural immune regulatory circuit. Here we identify neurotransmitter octopamine (OA) as an endogenous ligand for OCTR-1 in immune regulation and show that the OA-producing RIC neurons function in the OCTR-1 neural circuit to suppress innate immunity. RIC neurons are deactivated in the presence of pathogens but transiently activated by nonpathogenic bacteria. Our data support a model whereby an octopaminergic immunoinhibitory pathway is tonically active under normal conditions to maintain immunological homeostasis or suppress unwanted innate immune responses but downregulated upon pathogen infection to allow enhanced innate immunity. As excessive innate immune responses have been linked to a myriad of human health concerns, our study could potentially benefit the development of more-effective treatments for innate immune disorders. IMPORTANCE Insufficient or excessive immune responses to pathogen infection are major causes of disease. Increasing evidence indicates that the nervous system regulates the immune system to help maintain immunological homeostasis. However, the precise mechanisms of this regulation are largely unknown. Here we show the existence of an octopaminergic immunoinhibitory pathway in Caenorhabditis elegans. Our study results indicate that this pathway is tonically active under normal conditions to maintain immunological homeostasis or suppress unwanted innate immune responses but downregulated upon pathogen infection to allow enhanced innate immunity. As excessive innate immune responses have been linked to human health conditions such as Crohn's disease, rheumatoid arthritis, atherosclerosis, diabetes, and Alzheimer's disease, elucidating octopaminergic neural regulation of innate immunity could be helpful in the development of new treatments for innate immune diseases.
format	article
author	Durai Sellegounder Chung-Hsiang Yuan Phillip Wibisono Yiyong Liu Jingru Sun
author_facet	Durai Sellegounder Chung-Hsiang Yuan Phillip Wibisono Yiyong Liu Jingru Sun
author_sort	Durai Sellegounder
title	Octopaminergic Signaling Mediates Neural Regulation of Innate Immunity in <named-content content-type="genus-species">Caenorhabditis elegans</named-content>
title_short	Octopaminergic Signaling Mediates Neural Regulation of Innate Immunity in <named-content content-type="genus-species">Caenorhabditis elegans</named-content>
title_full	Octopaminergic Signaling Mediates Neural Regulation of Innate Immunity in <named-content content-type="genus-species">Caenorhabditis elegans</named-content>
title_fullStr	Octopaminergic Signaling Mediates Neural Regulation of Innate Immunity in <named-content content-type="genus-species">Caenorhabditis elegans</named-content>
title_full_unstemmed	Octopaminergic Signaling Mediates Neural Regulation of Innate Immunity in <named-content content-type="genus-species">Caenorhabditis elegans</named-content>
title_sort	octopaminergic signaling mediates neural regulation of innate immunity in <named-content content-type="genus-species">caenorhabditis elegans</named-content>
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/8aee613a45094d15884ab324fbc9c51d
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Octopaminergic Signaling Mediates Neural Regulation of Innate Immunity in <named-content content-type="genus-species">Caenorhabditis elegans</named-content>

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