Journal article
PPARα exacerbates Salmonella Typhimurium infection by modulating the immunometabolism and macrophage polarization
Gut microbes, v 16(1), p2419567
31 Dec 2024
PMID: 39508622
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Typhimurium (STm) is a causative pathogen for robust inflammatory gastrointestinal disease and can lead to systemic infection. Eicosanoids, bioactive lipid mediators, play a crucial role in modulating both the induction and resolution of inflammatory responses during an infection. A subset of eicosanoids activates PPARs, nuclear receptor/transcription factors that regulate fatty acid metabolism, lipid body formation, and macrophage function. In this study, we determined that mice lacking PPARα exhibited reduced inflammatory hallmarks of STm infection, including lower inflammatory gene expression, cecal inflammation, and bacterial dissemination, along with a significant increase in cecal eicosanoid metabolism compared to wildtype C57BL/6 mice. In macrophages, STm favored M2b-polarized macrophages for intracellular infection, leading to reduced arachidonic acid and ceramide production. Inhibition of fatty acid oxidation via Etomoxir in STm-infected macrophages reduced bacterial burdens and promoted cell death. In Etomoxir-treated wildtype mice, STm infection increased ceramide production, decreased inflammatory gene expression in the cecum, and increased the number of STm-containing M1 macrophages in mesenteric lymph nodes. These findings revealed a novel role for the lipid-immune signaling axis in
infections, providing significant insights into the lipid-mediated regulation of inflammation during bacterial infections in the gut.
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Details
- Title
- PPARα exacerbates Salmonella Typhimurium infection by modulating the immunometabolism and macrophage polarization
- Creators
- Jessica R Taddeo - Center for Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USANaomi Wilson - Temple UniversityAnita Kowal - Temple UniversityJoris Beld - Drexel University, Microbiology and ImmunologyKlein-Szanto Andres - Fox Chase Cancer CenterÇagla Tükel - Center for Microbiology and Immunology, Lewis Katz School of Medicine, Temple University, Philadelphia, PA, USAVincent C Tam - Temple University
- Publication Details
- Gut microbes, v 16(1), p2419567
- Publisher
- Taylor and Francis
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Microbiology and Immunology
- Web of Science ID
- WOS:001349434800001
- Scopus ID
- 2-s2.0-85209167136
- Other Identifier
- 991021970696904721
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InCites Highlights
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Gastroenterology & Hepatology
- Microbiology