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A pathogen-derived metabolite induces microglial activation via odorant receptors

Title
A pathogen-derived metabolite induces microglial activation via odorant receptors
Authors
Lee, NaHyeJae, YoonGyuKim, MinhyungCho, TaeHoLee, ChaeEunHong, Yu RiHyeon, Do YoungAhn, SanghyunKwon, HongmokKim, KyulJung, Jae HoonChae, SehyunShin, Jeong-OhBok, JinwoongByun, YoungjooHwang, DaeheeKoo, JaeHyung
DGIST Authors
Lee, NaHye; Jae, YoonGyu; Kim, Minhyung; Cho, TaeHo; Lee, ChaeEun; Hong, Yu Ri; Hyeon, Do Young; Ahn, Sanghyun; Kwon, Hongmok; Kim, Kyul; Jung, Jae Hoon; Chae, Sehyun; Shin, Jeong-Oh; Bok, Jinwoong; Byun, Youngjoo; Hwang, Daehee; Koo, JaeHyung
Issue Date
2020-09
Citation
FEBS Journal, 287(17), 3841-3870
Type
Article
Article Type
Article
Author Keywords
microglial activationnon-olfactory expressionodorant receptorpathogenic metabolite
Keywords
STREPTOCOCCUS-PNEUMONIAEOLFACTORY RECEPTORSPROTEINEXPRESSIONCELLSDESIGNSUSCEPTIBILITYDYSREGULATIONASTROCYTESINCREASES
ISSN
1742-464X
Abstract
Microglia (MG), the principal neuroimmune sentinels in the brain, continuously sense changes in their environment and respond to invading pathogens, toxins, and cellular debris, thereby affecting neuroinflammation. Microbial pathogens produce small metabolites that influence neuroinflammation, but the molecular mechanisms that determine whether pathogen-derived small metabolites affect microglial activation of neuroinflammation remain to be elucidated. We hypothesized that odorant receptors (ORs), the largest subfamily of G protein-coupled receptors, are involved in microglial activation by pathogen-derived small metabolites. We found that MG express high levels of two mouse ORs, Olfr110 and Olfr111, which recognize a pathogenic metabolite, 2-pentylfuran, secreted by Streptococcus pneumoniae. These interactions activate MG to engage in chemotaxis, cytokine production, phagocytosis, and reactive oxygen species generation. These effects were mediated through the Gαs–cyclic adenosine monophosphate–protein kinase A–extracellular signal-regulated kinase and Gβγ–phospholipase C–Ca2+ pathways. Taken together, our results reveal a novel interplay between the pathogen-derived metabolite and ORs, which has major implications for our understanding of microglial activation by pathogen recognition. Database: Model data are available in the PMDB database under the accession number PM0082389. © 2020 Federation of European Biochemical Societies
URI
http://hdl.handle.net/20.500.11750/11550
DOI
10.1111/febs.15234
Publisher
Wiley
Related Researcher
  • Author Koo, JaeHyung Ectopic Odorant Receptor Lab
  • Research Interests 장내미생물/감염균 유래 대사체를 통한 신경염증, 알츠하이머병, 우울증, 당뇨/비만, 대사체/수용체 상호작용에 의한 대사연구
Files:
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Collection:
Department of New BiologyEctopic Odorant Receptor Lab1. Journal Articles


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