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A pathogen-derived metabolite induces microglial activation via odorant receptors

Authors
 NaHye Lee  ;  YoonGyu Jae  ;  Minhyung Kim  ;  TaeHo Cho  ;  ChaeEun Lee  ;  Yu Ri Hong  ;  Do Young Hyeon  ;  Sanghyun Ahn  ;  Hongmok Kwon  ;  Kyul Kim  ;  Jae Hoon Jung  ;  Sehyun Chae  ;  Jeong-Oh Shin  ;  Jinwoong Bok  ;  Youngjoo Byun  ;  Daehee Hwang  ;  JaeHyung Koo 
Citation
 FEBS JOURNAL, Vol.287(17) : 3841-3870, 2020-09 
Journal Title
FEBS JOURNAL
ISSN
 1742-464X 
Issue Date
2020-09
MeSH
Animals ; CX3C Chemokine Receptor 1 / genetics ; Cells, Cultured ; Chemotaxis / drug effects ; Cytokines / biosynthesis ; Cytokines / genetics ; Furans / isolation & purification ; Furans / pharmacology* ; Gene Expression Regulation / drug effects ; Host-Pathogen Interactions ; Ligands ; Male ; Mice ; Mice, Inbred C57BL ; Microglia / drug effects* ; Microglia / metabolism ; Models, Molecular ; Molecular Structure ; Molecular Weight ; Phagocytosis / drug effects ; Protein Binding ; Protein Conformation ; RNA, Messenger / biosynthesis ; RNA, Messenger / genetics ; Reactive Oxygen Species / metabolism ; Receptors, Odorant / genetics ; Receptors, Odorant / physiology* ; Signal Transduction ; Streptococcus pneumoniae / metabolism* ; Superoxides / metabolism
Keywords
microglial activation ; non-olfactory expression ; odorant receptor ; pathogenic metabolite
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 G(alpha s)-cyclic adenosine monophosphate-protein kinase A-extracellular signal-regulated kinase and G(beta gamma)-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.
Full Text
https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.15234
DOI
10.1111/febs.15234
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Anatomy (해부학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Bok, Jin Woong(복진웅) ORCID logo https://orcid.org/0000-0003-1958-1872
Shin, Jeong Oh(신정오) ORCID logo https://orcid.org/0000-0002-6935-0936
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/190016
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