Interaction Between <i>Enterococcus faecalis</i> and <i>Fusobacterium nucleatum</i> Regulated Macrophage Transcriptional Profiling and Reprogrammed Cellular Immune and Metabolic Response
Refractory apical periodontitis (RAP), a persistent infection after root canal treatment, still has no effective treatment. <i>Enterococcus faecalis</i> (<i>E. faecalis</i>) and <i>Fusobacterium nucleatum</i> (<i>F. nucleatum</i>) are frequently detect...
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2025-06-01
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| author | Jingheng Liang Wenling Huang Poukei Chan Lihong Guo |
| author_facet | Jingheng Liang Wenling Huang Poukei Chan Lihong Guo |
| author_sort | Jingheng Liang |
| collection | DOAJ |
| description | Refractory apical periodontitis (RAP), a persistent infection after root canal treatment, still has no effective treatment. <i>Enterococcus faecalis</i> (<i>E. faecalis</i>) and <i>Fusobacterium nucleatum</i> (<i>F. nucleatum</i>) are frequently detected in the lesion. We previously found that coaggregation altered gene expression of <i>E. faecalis</i> and <i>F. nucleatum</i> and promoted immune evasion by suppressing pro-inflammatory cytokine secretion of macrophages (Mφs) while sustaining low-grade inflammation. In this study, we further investigated the synergistic effect of coaggregated <i>E. faecalis</i> and <i>F. nucleatum</i> on modulating Mφ immune and metabolic responses. Using transmission electron microscope, flow cytometry, RNA-seq and functional assays, we demonstrated that coaggregated <i>E. faecalis</i> and <i>F. nucleatum</i> caused nuclear shrinkage and increased mitochondria in Mφ while inducing M1 polarization, ROS production, and lipid accumulation of Mφ. The key driver genes causing the difference between single species-infected and coaggregated bacteria-infected Mφ mainly included IFN-stimulated genes and genes related to the chemokine signaling pathway. These findings indicate that the synergism of <i>E. faecalis</i> and <i>F. nucleatum</i> can regulate the immune and metabolic response of Mφ, offering novel insights into therapeutic targets for refractory apical periodontitis. |
| format | Article |
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| institution | DOAJ |
| issn | 2076-2607 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | MDPI AG |
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| series | Microorganisms |
| spelling | doaj-art-fd0d5e65d7e84c44acccf243c44e24b32025-08-20T03:16:21ZengMDPI AGMicroorganisms2076-26072025-06-01136135110.3390/microorganisms13061351Interaction Between <i>Enterococcus faecalis</i> and <i>Fusobacterium nucleatum</i> Regulated Macrophage Transcriptional Profiling and Reprogrammed Cellular Immune and Metabolic ResponseJingheng Liang0Wenling Huang1Poukei Chan2Lihong Guo3Hospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, ChinaHospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, ChinaHospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, ChinaHospital of Stomatology, Sun Yat-sen University, Guangzhou 510055, ChinaRefractory apical periodontitis (RAP), a persistent infection after root canal treatment, still has no effective treatment. <i>Enterococcus faecalis</i> (<i>E. faecalis</i>) and <i>Fusobacterium nucleatum</i> (<i>F. nucleatum</i>) are frequently detected in the lesion. We previously found that coaggregation altered gene expression of <i>E. faecalis</i> and <i>F. nucleatum</i> and promoted immune evasion by suppressing pro-inflammatory cytokine secretion of macrophages (Mφs) while sustaining low-grade inflammation. In this study, we further investigated the synergistic effect of coaggregated <i>E. faecalis</i> and <i>F. nucleatum</i> on modulating Mφ immune and metabolic responses. Using transmission electron microscope, flow cytometry, RNA-seq and functional assays, we demonstrated that coaggregated <i>E. faecalis</i> and <i>F. nucleatum</i> caused nuclear shrinkage and increased mitochondria in Mφ while inducing M1 polarization, ROS production, and lipid accumulation of Mφ. The key driver genes causing the difference between single species-infected and coaggregated bacteria-infected Mφ mainly included IFN-stimulated genes and genes related to the chemokine signaling pathway. These findings indicate that the synergism of <i>E. faecalis</i> and <i>F. nucleatum</i> can regulate the immune and metabolic response of Mφ, offering novel insights into therapeutic targets for refractory apical periodontitis.https://www.mdpi.com/2076-2607/13/6/1351<i>E. faecalis</i><i>F. nucleatum</i>bacterial interactionmacrophagerefractory apical periodontitis |
| spellingShingle | Jingheng Liang Wenling Huang Poukei Chan Lihong Guo Interaction Between <i>Enterococcus faecalis</i> and <i>Fusobacterium nucleatum</i> Regulated Macrophage Transcriptional Profiling and Reprogrammed Cellular Immune and Metabolic Response Microorganisms <i>E. faecalis</i> <i>F. nucleatum</i> bacterial interaction macrophage refractory apical periodontitis |
| title | Interaction Between <i>Enterococcus faecalis</i> and <i>Fusobacterium nucleatum</i> Regulated Macrophage Transcriptional Profiling and Reprogrammed Cellular Immune and Metabolic Response |
| title_full | Interaction Between <i>Enterococcus faecalis</i> and <i>Fusobacterium nucleatum</i> Regulated Macrophage Transcriptional Profiling and Reprogrammed Cellular Immune and Metabolic Response |
| title_fullStr | Interaction Between <i>Enterococcus faecalis</i> and <i>Fusobacterium nucleatum</i> Regulated Macrophage Transcriptional Profiling and Reprogrammed Cellular Immune and Metabolic Response |
| title_full_unstemmed | Interaction Between <i>Enterococcus faecalis</i> and <i>Fusobacterium nucleatum</i> Regulated Macrophage Transcriptional Profiling and Reprogrammed Cellular Immune and Metabolic Response |
| title_short | Interaction Between <i>Enterococcus faecalis</i> and <i>Fusobacterium nucleatum</i> Regulated Macrophage Transcriptional Profiling and Reprogrammed Cellular Immune and Metabolic Response |
| title_sort | interaction between i enterococcus faecalis i and i fusobacterium nucleatum i regulated macrophage transcriptional profiling and reprogrammed cellular immune and metabolic response |
| topic | <i>E. faecalis</i> <i>F. nucleatum</i> bacterial interaction macrophage refractory apical periodontitis |
| url | https://www.mdpi.com/2076-2607/13/6/1351 |
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