Eicosanoid-Activated PPARα Inhibits NFκB-Dependent Bacterial Clearance During Post-Influenza Superinfection
Genre
Journal articleDate
2022-07-04Author
Lucarelli, Ronald
Gorrochotegui, Norma

Taddeo, Jessica
Buttaro, Bettina

Beld, Joris
Tam, Vincent
Group
Center for Microbiology and Immunology (Temple University)Sol Sherry Thrombosis Research Center (Temple University)
Department
Microbiology, Immunology & InflammationSubject
InfluenzaStaphylococcus aureus
Eicosanoid
Cytochrome P450
Lipidomic
Innate immunity
Superinfection
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http://hdl.handle.net/20.500.12613/8135
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https://doi.org/10.3389/fcimb.2022.881462Abstract
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, Ppara–/– mice, which are partially protected in superinfection compared to C57BL/6 mice, have increased lipidomic responses and decreased M2-like macrophages during superinfection.Citation
Lucarelli R, Gorrochotegui-Escalante N, Taddeo J, Buttaro B, Beld J and Tam V (2022) Eicosanoid-Activated PPARα Inhibits NFκB-Dependent Bacterial Clearance During Post-Influenza Superinfection. Front. Cell. Infect. Microbiol. 12:881462. doi: 10.3389/fcimb.2022.881462Citation to related work
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Frontiers in Cellular and Infection Microbiology, Vol. 12ADA compliance
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