Eicosanoid-Activated PPARα Inhibits NFκB-Dependent Bacterial Clearance During Post-Influenza Superinfection.
Cytochrome P450
Staphylococcus aureus
Superinfection
eicosanoid
influenza
innate immunity
lipidomic
Journal
Frontiers in cellular and infection microbiology
ISSN: 2235-2988
Titre abrégé: Front Cell Infect Microbiol
Pays: Switzerland
ID NLM: 101585359
Informations de publication
Date de publication:
2022
2022
Historique:
received:
22
02
2022
accepted:
31
05
2022
entrez:
21
7
2022
pubmed:
22
7
2022
medline:
23
7
2022
Statut:
epublish
Résumé
Secondary bacterial infection (superinfection) post influenza is a serious clinical complication often leading to pneumonia and death. Eicosanoids are bioactive lipid mediators that play critical roles in the induction and resolution of inflammation. CYP450 lipid metabolites are anti-inflammatory lipid mediators that are produced at an excessive level during superinfection potentiating the vulnerability to secondary bacterial infection. Using Nanostring nCounter technology, we have defined the targeted transcriptional response where CYP450 metabolites dampen the Toll-like receptor signaling in macrophages. CYP450 metabolites are endogenous ligands for the nuclear receptor and transcription factor, PPARα. Activation of PPARα hinders NFκB p65 activities by altering its phosphorylation and nuclear translocation during TLR stimulation. Additionally, activation of PPARα inhibited anti-bacterial activities and enhanced macrophage polarization to an anti-inflammatory subtype (M2b). Lastly,
Identifiants
pubmed: 35860381
doi: 10.3389/fcimb.2022.881462
pmc: PMC9289478
doi:
Substances chimiques
Eicosanoids
0
NF-kappa B
0
PPAR alpha
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
881462Subventions
Organisme : NIAID NIH HHS
ID : R01 AI168550
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI142278
Pays : United States
Informations de copyright
Copyright © 2022 Lucarelli, Gorrochotegui-Escalante, Taddeo, Buttaro, Beld and Tam.
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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