Monocyte metabolic reprogramming promotes pro-inflammatory activity and Staphylococcus aureus biofilm clearance.

PLoS Pathogens
Kelsey J YamadaTammy Kielian

Abstract

Biofilm-associated prosthetic joint infections (PJIs) cause significant morbidity due to their recalcitrance to immune-mediated clearance and antibiotics, with Staphylococcus aureus (S. aureus) among the most prevalent pathogens. We previously demonstrated that S. aureus biofilm-associated monocytes are polarized to an anti-inflammatory phenotype and the adoptive transfer of pro-inflammatory macrophages attenuated biofilm burden, highlighting the critical role of monocyte/macrophage inflammatory status in dictating biofilm persistence. The inflammatory properties of leukocytes are linked to their metabolic state, and here we demonstrate that biofilm-associated monocytes exhibit a metabolic bias favoring oxidative phosphorylation (OxPhos) and less aerobic glycolysis to facilitate their anti-inflammatory activity and biofilm persistence. To shift monocyte metabolism in vivo and reprogram cells to a pro-inflammatory state, a nanoparticle approach was utilized to deliver the OxPhos inhibitor oligomycin to monocytes. Using a mouse model of S. aureus PJI, oligomycin nanoparticles were preferentially internalized by monocytes, which significantly reduced S. aureus biofilm burden by altering metabolism and promoting the pro-inflammator...Continue Reading

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Citations

Aug 28, 2020·Frontiers in Microbiology·Timothy J Foster
Sep 13, 2020·Toxins·Alice Prince, Tania Wong Fok Lung
Oct 21, 2020·EMBO Molecular Medicine·Lara GibelliniAndrea Cossarizza
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Mar 13, 2021·Frontiers in Immunology·Sharon Db de MoraisTammy Kielian
Jun 11, 2021·Frontiers in Immunology·Vanessa ChilundaJoan W Berman

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Methods Mentioned

BETA
total hip arthroplasty
flow cytometry
FACS
ELISA
protein assay
dynamic light scattering

Key Resources (RRID) Mentioned

IMSR_CRL
AB_493342
AB_2564164
AB_2650770
AB_312977
AB_2251161
AB_893478
AB_493705
AB_493535
AB_1186099

Software Mentioned

MetaboAnalyst
BD FACSDiva
GraphPad Prism
ARRIVE

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