Delivery of Periodontopathogenic Extracellular Vesicles to Brain Monocytes and Microglial IL-6 Promotion by RNA Cargo
Gram-negative bacterial extracellular vesicles (EVs), also known as outer membrane vesicles (OMVs), are secreted from bacterial cells and have attracted research attention due to their role in cell-to-cell communication. During OMV secretion, a variety of cargo such as extracellular RNA (exRNA) is l...
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| Format: | Article |
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Frontiers Media S.A.
2020-11-01
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| Series: | Frontiers in Molecular Biosciences |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmolb.2020.596366/full |
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| author | Jae Yeong Ha Song-Yi Choi Ji Hye Lee Su-Hyung Hong Heon-Jin Lee Heon-Jin Lee |
| author_facet | Jae Yeong Ha Song-Yi Choi Ji Hye Lee Su-Hyung Hong Heon-Jin Lee Heon-Jin Lee |
| author_sort | Jae Yeong Ha |
| collection | DOAJ |
| description | Gram-negative bacterial extracellular vesicles (EVs), also known as outer membrane vesicles (OMVs), are secreted from bacterial cells and have attracted research attention due to their role in cell-to-cell communication. During OMV secretion, a variety of cargo such as extracellular RNA (exRNA) is loaded into the OMV. The involvement of exRNAs from a range of bacteria has been identified in several diseases, however, their mechanism of action has not been elucidated. We have recently demonstrated that OMVs secreted by the periodontopathogen Aggregatibacter actinomycetemcomitans can cross the blood–brain barrier (BBB) and that its exRNA cargo could promote the secretion of proinflammatory cytokines in the brain. However, it was unclear whether the brain immune cells could actually take up bacterial OMVs, which originate outside of the brain, in an appropriate immune response. In the present study, using monocyte-specific live CX3CR1-GFP mice, we visualized OMV-colocalized meningeal macrophages and microglial cells into which bacterial OMVs had been loaded and intravenously injected through tail veins. Our results suggested that meningeal macrophages uptake BBB-crossed OMVs earlier than do cortex microglia. BV2 cells (a murine microglia cell line) and exRNAs were also visualized after OMV treatment and their proinflammatory cytokine levels were observed. Interleukin (IL)-6 and NF-κB of BV2 cells were activated by A. actinomycetemcomitans exRNAs but not by OMV DNA cargo. Altogether, these findings indicate that OMVs can successfully deliver exRNAs into brain monocyte/microglial cells and cause neuroinflammation, implicating a novel pathogenic mechanism in neuroinflammatory diseases. |
| first_indexed | 2024-12-12T13:42:26Z |
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| id | doaj.art-8069f78fe3af4618b929c21931a38da7 |
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| language | English |
| last_indexed | 2024-12-12T13:42:26Z |
| publishDate | 2020-11-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Molecular Biosciences |
| spelling | doaj.art-8069f78fe3af4618b929c21931a38da72022-12-22T00:22:45ZengFrontiers Media S.A.Frontiers in Molecular Biosciences2296-889X2020-11-01710.3389/fmolb.2020.596366596366Delivery of Periodontopathogenic Extracellular Vesicles to Brain Monocytes and Microglial IL-6 Promotion by RNA CargoJae Yeong Ha0Song-Yi Choi1Ji Hye Lee2Su-Hyung Hong3Heon-Jin Lee4Heon-Jin Lee5Department of Microbiology and Immunology, School of Dentistry, Kyungpook National University, Daegu, South KoreaDepartment of Microbiology and Immunology, School of Dentistry, Kyungpook National University, Daegu, South KoreaDepartment of Oral Pathology, Dental and Life Science Institute, School of Dentistry, Pusan National University, Yangsan, South KoreaDepartment of Microbiology and Immunology, School of Dentistry, Kyungpook National University, Daegu, South KoreaDepartment of Microbiology and Immunology, School of Dentistry, Kyungpook National University, Daegu, South KoreaBrain Science and Engineering Institute, Kyungpook National University, Daegu, South KoreaGram-negative bacterial extracellular vesicles (EVs), also known as outer membrane vesicles (OMVs), are secreted from bacterial cells and have attracted research attention due to their role in cell-to-cell communication. During OMV secretion, a variety of cargo such as extracellular RNA (exRNA) is loaded into the OMV. The involvement of exRNAs from a range of bacteria has been identified in several diseases, however, their mechanism of action has not been elucidated. We have recently demonstrated that OMVs secreted by the periodontopathogen Aggregatibacter actinomycetemcomitans can cross the blood–brain barrier (BBB) and that its exRNA cargo could promote the secretion of proinflammatory cytokines in the brain. However, it was unclear whether the brain immune cells could actually take up bacterial OMVs, which originate outside of the brain, in an appropriate immune response. In the present study, using monocyte-specific live CX3CR1-GFP mice, we visualized OMV-colocalized meningeal macrophages and microglial cells into which bacterial OMVs had been loaded and intravenously injected through tail veins. Our results suggested that meningeal macrophages uptake BBB-crossed OMVs earlier than do cortex microglia. BV2 cells (a murine microglia cell line) and exRNAs were also visualized after OMV treatment and their proinflammatory cytokine levels were observed. Interleukin (IL)-6 and NF-κB of BV2 cells were activated by A. actinomycetemcomitans exRNAs but not by OMV DNA cargo. Altogether, these findings indicate that OMVs can successfully deliver exRNAs into brain monocyte/microglial cells and cause neuroinflammation, implicating a novel pathogenic mechanism in neuroinflammatory diseases.https://www.frontiersin.org/articles/10.3389/fmolb.2020.596366/fullperiodontitissmall RNAextracellular vesicleAggregatibacter actinomycetemcomitansouter membrane vesicle |
| spellingShingle | Jae Yeong Ha Song-Yi Choi Ji Hye Lee Su-Hyung Hong Heon-Jin Lee Heon-Jin Lee Delivery of Periodontopathogenic Extracellular Vesicles to Brain Monocytes and Microglial IL-6 Promotion by RNA Cargo Frontiers in Molecular Biosciences periodontitis small RNA extracellular vesicle Aggregatibacter actinomycetemcomitans outer membrane vesicle |
| title | Delivery of Periodontopathogenic Extracellular Vesicles to Brain Monocytes and Microglial IL-6 Promotion by RNA Cargo |
| title_full | Delivery of Periodontopathogenic Extracellular Vesicles to Brain Monocytes and Microglial IL-6 Promotion by RNA Cargo |
| title_fullStr | Delivery of Periodontopathogenic Extracellular Vesicles to Brain Monocytes and Microglial IL-6 Promotion by RNA Cargo |
| title_full_unstemmed | Delivery of Periodontopathogenic Extracellular Vesicles to Brain Monocytes and Microglial IL-6 Promotion by RNA Cargo |
| title_short | Delivery of Periodontopathogenic Extracellular Vesicles to Brain Monocytes and Microglial IL-6 Promotion by RNA Cargo |
| title_sort | delivery of periodontopathogenic extracellular vesicles to brain monocytes and microglial il 6 promotion by rna cargo |
| topic | periodontitis small RNA extracellular vesicle Aggregatibacter actinomycetemcomitans outer membrane vesicle |
| url | https://www.frontiersin.org/articles/10.3389/fmolb.2020.596366/full |
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