Allatostatin C modulates nociception and immunity in Drosophila

Abstract Bacterial induced inflammatory responses cause pain through direct activation of nociceptive neurons, and the ablation of these neurons leads to increased immune infiltration. In this study, we investigated nociceptive-immune interactions in Drosophila and the role these interactions play d...

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Autores principales:	Nathaniel D. Bachtel, Gary A. Hovsepian, Douglas F. Nixon, Ioannis Eleftherianos
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0fb0032bddbd4f11ad1aabbe2554da78
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spelling	oai:doaj.org-article:0fb0032bddbd4f11ad1aabbe2554da782021-12-02T12:32:21ZAllatostatin C modulates nociception and immunity in Drosophila10.1038/s41598-018-25855-12045-2322https://doaj.org/article/0fb0032bddbd4f11ad1aabbe2554da782018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25855-1https://doaj.org/toc/2045-2322Abstract Bacterial induced inflammatory responses cause pain through direct activation of nociceptive neurons, and the ablation of these neurons leads to increased immune infiltration. In this study, we investigated nociceptive-immune interactions in Drosophila and the role these interactions play during pathogenic bacterial infection. After bacterial infection, we found robust upregulation of ligand-gated ion channels and allatostatin receptors involved in nociception, which potentially leads to hyperalgesia. We further found that Allatostatin-C Receptor 2 (AstC-R2) plays a crucial role in host survival during infection with the pathogenic bacterium Photorhabdus luminescens. Upon examination of immune signaling in AstC-R2 deficient mutants, we demonstrated that Allatostatin-C Receptor 2 specifically inhibits the Immune deficiency pathway, and knockdown of AstC-R2 leads to overproduction of antimicrobial peptides related to this pathway and decreased host survival. This study provides mechanistic insights into the importance of microbe-nociceptor interactions during bacterial challenge. We posit that Allatostatin C is an immunosuppressive substance released by nociceptors or Drosophila hemocytes that dampens IMD signaling in order to either prevent immunopathology or to reduce unnecessary metabolic cost after microbial stimulation. AstC-R2 also acts to dampen thermal nociception in the absence of infection, suggesting an intrinsic neuronal role in mediating these processes during homeostatic conditions. Further examination into the signaling mechanisms by which Allatostatin-C alters immunity and nociception in Drosophila may reveal conserved pathways which can be utilized towards therapeutically targeting inflammatory pain and chronic inflammation.Nathaniel D. BachtelGary A. HovsepianDouglas F. NixonIoannis EleftherianosNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-11 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nathaniel D. Bachtel Gary A. Hovsepian Douglas F. Nixon Ioannis Eleftherianos Allatostatin C modulates nociception and immunity in Drosophila
description	Abstract Bacterial induced inflammatory responses cause pain through direct activation of nociceptive neurons, and the ablation of these neurons leads to increased immune infiltration. In this study, we investigated nociceptive-immune interactions in Drosophila and the role these interactions play during pathogenic bacterial infection. After bacterial infection, we found robust upregulation of ligand-gated ion channels and allatostatin receptors involved in nociception, which potentially leads to hyperalgesia. We further found that Allatostatin-C Receptor 2 (AstC-R2) plays a crucial role in host survival during infection with the pathogenic bacterium Photorhabdus luminescens. Upon examination of immune signaling in AstC-R2 deficient mutants, we demonstrated that Allatostatin-C Receptor 2 specifically inhibits the Immune deficiency pathway, and knockdown of AstC-R2 leads to overproduction of antimicrobial peptides related to this pathway and decreased host survival. This study provides mechanistic insights into the importance of microbe-nociceptor interactions during bacterial challenge. We posit that Allatostatin C is an immunosuppressive substance released by nociceptors or Drosophila hemocytes that dampens IMD signaling in order to either prevent immunopathology or to reduce unnecessary metabolic cost after microbial stimulation. AstC-R2 also acts to dampen thermal nociception in the absence of infection, suggesting an intrinsic neuronal role in mediating these processes during homeostatic conditions. Further examination into the signaling mechanisms by which Allatostatin-C alters immunity and nociception in Drosophila may reveal conserved pathways which can be utilized towards therapeutically targeting inflammatory pain and chronic inflammation.
format	article
author	Nathaniel D. Bachtel Gary A. Hovsepian Douglas F. Nixon Ioannis Eleftherianos
author_facet	Nathaniel D. Bachtel Gary A. Hovsepian Douglas F. Nixon Ioannis Eleftherianos
author_sort	Nathaniel D. Bachtel
title	Allatostatin C modulates nociception and immunity in Drosophila
title_short	Allatostatin C modulates nociception and immunity in Drosophila
title_full	Allatostatin C modulates nociception and immunity in Drosophila
title_fullStr	Allatostatin C modulates nociception and immunity in Drosophila
title_full_unstemmed	Allatostatin C modulates nociception and immunity in Drosophila
title_sort	allatostatin c modulates nociception and immunity in drosophila
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/0fb0032bddbd4f11ad1aabbe2554da78
work_keys_str_mv	AT nathanieldbachtel allatostatincmodulatesnociceptionandimmunityindrosophila AT garyahovsepian allatostatincmodulatesnociceptionandimmunityindrosophila AT douglasfnixon allatostatincmodulatesnociceptionandimmunityindrosophila AT ioanniseleftherianos allatostatincmodulatesnociceptionandimmunityindrosophila
_version_	1718394079798099968

Allatostatin C modulates nociception and immunity in Drosophila

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