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Periodontitis promotes bacterial extracellular vesicle-induced neuroinflammation in the brain and trigeminal ganglion.
Ha, Jae Yeong; Seok, Jiwon; Kim, Suk-Jeong; Jung, Hye-Jin; Ryu, Ka-Young; Nakamura, Michiko; Jang, Il-Sung; Hong, Su-Hyung; Lee, Youngkyun; Lee, Heon-Jin.
Afiliación
  • Ha JY; Department of Microbiology and Immunology, School of Dentistry, Kyungpook National University, Daegu, Korea.
  • Seok J; Craniofacial Nerve-Bone Network Research Center, Kyungpook National University, Daegu, Korea.
  • Kim SJ; Department of Biochemistry, School of Dentistry, Kyungpook National University, Daegu, Korea.
  • Jung HJ; Department of Microbiology and Immunology, School of Dentistry, Kyungpook National University, Daegu, Korea.
  • Ryu KY; Craniofacial Nerve-Bone Network Research Center, Kyungpook National University, Daegu, Korea.
  • Nakamura M; Department of Biochemistry, School of Dentistry, Kyungpook National University, Daegu, Korea.
  • Jang IS; Craniofacial Nerve-Bone Network Research Center, Kyungpook National University, Daegu, Korea.
  • Hong SH; Department of Biochemistry, School of Dentistry, Kyungpook National University, Daegu, Korea.
  • Lee Y; Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Korea.
  • Lee HJ; Brain Science & Engineering Institute, Kyungpook National University, Daegu, Korea.
PLoS Pathog ; 19(10): e1011743, 2023 Oct.
Article en En | MEDLINE | ID: mdl-37871107
Gram-negative bacteria derived extracellular vesicles (EVs), also known as outer membrane vesicles, have attracted significant attention due to their pathogenic roles in various inflammatory diseases. We recently demonstrated that EVs secreted by the periodontopathogen Aggregatibacter actinomycetemcomitans (Aa) can cross the blood-brain barrier (BBB) and that their extracellular RNA cargo can promote the secretion of proinflammatory cytokines, such as IL-6 and TNF-α, in the brain. To gain more insight into the relationship between periodontal disease (PD) and neuroinflammatory diseases, we investigated the effect of Aa EVs in a mouse model of ligature-induced PD. When EVs were administered through intragingival injection or EV-soaked gel, proinflammatory cytokines were strongly induced in the brains of PD mice. The use of TLR (Toll-like receptor)-reporter cell lines and MyD88 knockout mice confirmed that the increased release of cytokines was triggered by Aa EVs via TLR4 and TLR8 signaling pathways and their downstream MyD88 pathway. Furthermore, the injection of EVs through the epidermis and gingiva resulted in the direct retrograde transfer of Aa EVs from axon terminals to the cell bodies of trigeminal ganglion (TG) neurons and the subsequent activation of TG neurons. We also found that the Aa EVs changed the action potential of TG neurons. These findings suggest that EVs derived from periodontopathogens such as Aa might be involved in pathogenic pathways for neuroinflammatory diseases, neuropathic pain, and other systemic inflammatory symptoms as a comorbidity of periodontitis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Periodontales / Periodontitis / Vesículas Extracelulares Límite: Animals Idioma: En Revista: PLoS Pathog Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedades Periodontales / Periodontitis / Vesículas Extracelulares Límite: Animals Idioma: En Revista: PLoS Pathog Año: 2023 Tipo del documento: Article Pais de publicación: Estados Unidos