AI Article Synopsis
- The text discusses the bacterial species associated with periodontitis and its outer membrane vesicles (OMVs), which are thought to contribute to the bacteria's ability to cause disease.
- The study compares how macrophages, which are immune cells, respond to either the bacteria or its OMVs, with the latter causing greater immune mediator production and shifting macrophage metabolism to glycolysis.
- The findings highlight that while the bacteria do not activate inflammasomes leading to cell death, the OMVs do trigger significant inflammatory responses and cell death processes, suggesting their important role in chronic periodontitis pathology.
Article Abstract
is one of the bacterial species most closely associated with periodontitis and can shed large numbers of outer membrane vesicles (OMVs), which are increasingly thought to play a significant role in bacterial virulence and pathogenicity. Macrophages are amongst the first immune cells to respond to bacteria and their products, so we sought to directly compare the response of macrophages to or its purified OMVs. Macrophages stimulated with OMVs produced large amounts of TNFα, IL-12p70, IL-6, IL-10, IFNβ, and nitric oxide compared to cells infected with , which produced very low levels of these mediators. Both and OMVs induced a shift in macrophage metabolism from oxidative phosphorylation (OXPHOS) to glycolysis, which was supported by enhanced lactate release, decreased mitochondrial oxygen consumption with reduced spare respiratory capacity, as well as increased mitochondrial reactive oxygen species (ROS) production. Corresponding to this metabolic shift, gene expression analysis of macrophages infected with or stimulated with OMVs revealed a broad transcriptional upregulation of genes critical to glycolysis and a downregulation of genes associated with the TCA cycle. Upon examination of inflammasome signaling and pyroptosis it was found that did not activate the inflammasome in macrophages as the mature forms of caspase-1, IL-1β, and IL-18 were not detected and there was no extracellular release of lactate dehydrogenase (LDH) or 7-AAD staining. In comparison, macrophages stimulated with OMVs potently activated caspase-1, produced large amounts of IL-1β, IL-18, released LDH, and were positive for 7-AAD indicative of pyroptotic cell death. These data directly quantitate the distinct effects of and its OMVs on macrophage inflammatory phenotype, mitochondrial function, inflammasome activation, and pyroptotic cell death that may have potential implications for their roles in chronic periodontitis.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5543041 | PMC |
| http://dx.doi.org/10.3389/fcimb.2017.00351 | DOI Listing |
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