Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Biomedical Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 2049-9434 Online ISSN: 2049-9442
Journal Cover
July-2025 Volume 23 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
July-2025 Volume 23 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

Modifying immune cells using mouse bone marrow‑derived cell exosomes during administration of heat‑killed lactic acid bacterium Enterococcus faecalis

  • Authors:
    • Koji Nakao
    • Tomoe Matsuo
    • Iwao Shimaoka
    • Kosuke Hara
  • View Affiliations / Copyright

    Affiliations: Academic Division, NUTRI Co., Ltd., Shiba, Tokyo 108‑0014, Japan
    Copyright: © Nakao et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 4.0].
  • Article Number: 114
    |
    Published online on: May 13, 2025
       https://doi.org/10.3892/br.2025.1992
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

Previously, the mechanism underlying the immunostimulatory effect of orally administered heat‑killed Enterococcus faecalis (HkEf) mediated by exosomes secreted after intestinal macrophage phagocytosis was clarified. In the present study, mouse bone marrow‑derived dendritic cells (DCs) were used as intestinal DCs. In vitro studies evaluating the response of mouse spleen cells to exosomes purified and isolated from intestinal DCs stimulated with HkEf showed a significant increase in standard DCs and plasmacytoid DCs (pDCs), indicating a positive effect on DCs, mainly pDCs, and possibly contributing to their immunostimulatory effects. The microRNAs (miRNAs) of exosome fractions derived from intestinal DCs and macrophages were also examined using bone marrow progenitor cells. HkEf stimulation released miRNA‑rich exosomes, which acted as an immune response signal mediator, and increased various miRNAs other than miR‑146 that are essential for refilling innate immune cells. In the present study, the effect mediated by miRNA‑rich exosomes on the distant immune system from intestinal immunity (macrophages, DCs) was observed via orally administered HkEf, a Lactobacillus preparation. The findings of the present study revealed that this mechanism can potentially prevent systemic infection.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Inatomi T and Otomaru K: Effects of heat-killed Enterococcus faecalis T-110 supplementation on gut immunity, gut flora, and intestinal infection in naturally aged hamsters. PLoS One. 15(e0240773)2020.PubMed/NCBI View Article : Google Scholar

2 

Watanabe T, Hayashi K, Kan T, Ohwaki M and Kawahara T: Anti-influenza virus effects of Enterococcus faecalis KH2 and Lactobacillus plantarum SNK12 RNA. Biosci Microbiota Food Health. 40:43–49. 2021.PubMed/NCBI View Article : Google Scholar

3 

Hara K, Nakao K and Kawaguchi S: Efficacy of heat-killed lactic acid bacteria Enterococcus faecalis on methicillin-resistant Staphylococcus aureus (MRSA) infected mice. J New Rem Clin. 67:35–44. 2018.(In Japanese).

4 

Nakao K, Hara K, Matsuo T and Kawauchi S: Effects of heat-killed lactic acid bacteria Enterococcus faecalis on life-threatening antibiotic-resistant bacteria in animal models. J New Rem Clin. 69:276–287. 2020.(In Japanese).

5 

Matsuo T, Nakao K, Hara K and Kawaguchi S: Blood-derived exosomes released after the oral administration of heat-killed Enterococcus faecalis activate immunity. Biosci Biotechnol Biochem. 86:1699–1704. 2022.PubMed/NCBI View Article : Google Scholar

6 

Inotsuka R, Udono M, Yamatsu A, Kim M and Katakura Y: Exosome-mediated activation of neuronal cells triggered by γ-aminobutyric acid (GABA). Biosci Microb Food Health. 40:43–49. 2021.PubMed/NCBI View Article : Google Scholar

7 

Inotsuka R, Uchimura K, Yamatsu A, Kim M and Katakura Y: γ-Aminobutyric acid (GABA) activates neuronal cells by inducing the secretion of exosomes from intestinal cells. Food Funct. 11:9285–9290. 2020.PubMed/NCBI View Article : Google Scholar

8 

Sugihara Y, Onoue S, Tashiro K, Sato M, Hasegawa T and Katakura Y: Carnosine induces intestinal cells to secrete exosomes that activate neuronal cells. PLoS One. 14(e0217394)2019.PubMed/NCBI View Article : Google Scholar

9 

Hemmi H, Kaisho T, Takeda K and Akira S: The roles of Toll-like receptor 9, MyD88, and DNA-dependent protein kinase catalytic subunit in the effects of two distinct CpG DNAs on dendritic cell subsets. J Immunol. 170:3059–3064. 2003.PubMed/NCBI View Article : Google Scholar

10 

Steinman RM: Decisions about dendritic cells: Past, present, and future. Annu Rev Immunol. 30:1–22. 2012.PubMed/NCBI View Article : Google Scholar

11 

Gilliet M, Boonstra A, Paturel C, Antonenko S, Xu XL, Trinchieri G, O'Garra A and Liu YJ: The development of murine plasmacytoid dendritic cell precursors is differentially regulated by FLT3-ligand and granulocyte/macrophage colony-stimulating factor. J Exp Med. 195:953–958. 2002.PubMed/NCBI View Article : Google Scholar

12 

Taganov KD, Boldin MP, Chang KJ and Baltimore D: NF-kappaB-dependent induction of microRNA miR-146, an inhibitor targeted to signaling proteins of innate immune responses. Proc Natl Acad Sci USA. 103:12481–12486. 2006.PubMed/NCBI View Article : Google Scholar

13 

Starczynowski DT, Kuchenbauer F, Wegrzyn J, Rouhi A, Petriv O, Hansen CL, Humphries RK and Karsan A: MicroRNA-146a disrupts hematopoietic differentiation and survival. Exp Hematol. 39:167–178.e4. 2011.PubMed/NCBI View Article : Google Scholar

14 

Ueda Y, Kondo M and Kelsoe G: Inflammation and the reciprocal production of granulocytes and lymphocytes in bone marrow. J Exp Med. 201:1771–1780. 2005.PubMed/NCBI View Article : Google Scholar

15 

Nagai Y, Garrett KP, Ohta S, Bahrun U, Kouro T, Akira S, Takatsu K and Kincade PW: Toll-like receptors on hematopoietic progenitor cells stimulate innate immune system replenishment. Immunity. 24:801–812. 2006.PubMed/NCBI View Article : Google Scholar

16 

Han YC, Park CY, Bhagat G, Zhang J, Wang Y, Fan JB, Liu M, Zou Y, Weissman IL and Gu H: microRNA-29a induces aberrant self-renewal capacity in hematopoietic progenitors, biased myeloid development, and acute myeloid leukemia. J Exp Med. 207:475–489. 2010.PubMed/NCBI View Article : Google Scholar

17 

Karrich JJ, Jachimowski LC, Libouban M, Iyer A, Brandwijk K, Taanman-Kueter EW, Nagasawa M, de Jong EC, Uittenbogaart CH and Blom B: MicroRNA-146a regulates survival and maturation of human plasmacytoid dendritic cells. Blood. 122:3001–3009. 2013.PubMed/NCBI View Article : Google Scholar

18 

Hong Y, Wu J, Zhao J, Wang H, Liu Y, Chen T, Kan X, Tao Q, Shen X, Yan K and Zhai Z: miR-29b and miR-29c are involved in Toll-like receptor control of glucocorticoid-induced apoptosis in human plasmacytoid dendritic cells. PLoS One. 8(e69926)2013.PubMed/NCBI View Article : Google Scholar

19 

Buscaglia LEB and Li Y: Apoptosis and the target genes of microRNA-21. Chin J Cancer. 30:371–380. 2011.PubMed/NCBI View Article : Google Scholar

20 

Huang A, Yang Y, Chen S, Xia F, Sun D, Fang D, Xiong S, Jin L and Zhang J: MiR-34a promotes DCs development and inhibits their function on T cell activation by targeting WNT1. Oncotarget. 8:17191–17201. 2017.PubMed/NCBI View Article : Google Scholar

21 

Hashimi ST, Fulcher JA, Chang MH, Gov L, Wang S and Lee B: MicroRNA profiling identifies miR-34a and miR-21 and their target genes JAG1 and WNT1 in the coordinate regulation of dendritic cell differentiation. Blood. 114:404–414. 2009.PubMed/NCBI View Article : Google Scholar

22 

Li HS, Greeley N, Sugimoto N, Liu YJ and Watowich SS: miR-22 controls Irf8 mRNA abundance and murine dendritic cell development. PLoS One. 7(e52341)2012.PubMed/NCBI View Article : Google Scholar

23 

Kuipers H, Schnorfeil FM and Brocker T: Differentially expressed microRNAs regulate plasmacytoid vs conventional dendritic cell development. Mol Immunol. 48:333–340. 2010.PubMed/NCBI View Article : Google Scholar

24 

Lu C, Huang X, Zhang X, Roensch K, Cao Q, Nakayama KI, Blazar BR, Zeng Y and Zhou X: miR-221 and miR-155 regulate human dendritic cell development, apoptosis, and IL-12 production through targeting of p27kip1, KPC1, and SOCS-1. Blood. 117:4293–4303. 2011.PubMed/NCBI View Article : Google Scholar

25 

Zhou H, Xiao J, Wu N, Liu C, Xu J, Liu F and Wu L: MicroRNA-223 regulates the differentiation and function of intestinal dendritic cells and macrophages by targeting C/EBPβ. Cell Rep. 13:1149–1160. 2015.PubMed/NCBI View Article : Google Scholar

26 

Bros M, Youns M, Kollek V, Buchmüller D, Bollmann F, Seo EJ, Schupp J, Montermann E, Usanova S, Kleinert H, et al: Differentially tolerized mouse antigen presenting cells share a common miRNA signature including enhanced mmu-miR-223-3p expression which is sufficient to imprint a Protolerogenic State. Front Pharmacol. 9(915)2018.PubMed/NCBI View Article : Google Scholar

27 

Yuan X, Berg N, Lee JW, Le TT, Neudecker V, Jing N and Eltzschig H: MicroRNA miR-223 as regulator of innate immunity. J Leukoc Biol. 104:515–524. 2018.PubMed/NCBI View Article : Google Scholar

28 

Zhu MX, Wan WL, Hu K, Wang YF, Wang J, Zhu XW, Yan XX, Jing HM and Ke XY: MicroRNA-223 regulates the differentiation of human embryonic stem cells to dendritic cells. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 25:1275–1282. 2017.PubMed/NCBI View Article : Google Scholar : (In Chinese).

29 

Fontana L, Pelosi E, Greco P, Racanicchi S, Testa U, Liuzzi F, Croce CM, Brunetti E, Grignani F and Peschle C: MicroRNAs 17-5p-20a-106a control monocytopoiesis through AML1 targeting and M-CSF receptor upregulation. Nat Cell Biol. 9:775–787. 2007.PubMed/NCBI View Article : Google Scholar

30 

Kim CH: Homeostatic and pathogenic extramedullary hematopoiesis. J Blood Med. 1:13–19. 2010.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Nakao K, Matsuo T, Shimaoka I and Hara K: Modifying immune cells using mouse bone marrow‑derived cell exosomes during administration of heat‑killed lactic acid bacterium <em>Enterococcus faecalis</em>. Biomed Rep 23: 114, 2025.
APA
Nakao, K., Matsuo, T., Shimaoka, I., & Hara, K. (2025). Modifying immune cells using mouse bone marrow‑derived cell exosomes during administration of heat‑killed lactic acid bacterium <em>Enterococcus faecalis</em>. Biomedical Reports, 23, 114. https://doi.org/10.3892/br.2025.1992
MLA
Nakao, K., Matsuo, T., Shimaoka, I., Hara, K."Modifying immune cells using mouse bone marrow‑derived cell exosomes during administration of heat‑killed lactic acid bacterium <em>Enterococcus faecalis</em>". Biomedical Reports 23.1 (2025): 114.
Chicago
Nakao, K., Matsuo, T., Shimaoka, I., Hara, K."Modifying immune cells using mouse bone marrow‑derived cell exosomes during administration of heat‑killed lactic acid bacterium <em>Enterococcus faecalis</em>". Biomedical Reports 23, no. 1 (2025): 114. https://doi.org/10.3892/br.2025.1992
Copy and paste a formatted citation
x
Spandidos Publications style
Nakao K, Matsuo T, Shimaoka I and Hara K: Modifying immune cells using mouse bone marrow‑derived cell exosomes during administration of heat‑killed lactic acid bacterium <em>Enterococcus faecalis</em>. Biomed Rep 23: 114, 2025.
APA
Nakao, K., Matsuo, T., Shimaoka, I., & Hara, K. (2025). Modifying immune cells using mouse bone marrow‑derived cell exosomes during administration of heat‑killed lactic acid bacterium <em>Enterococcus faecalis</em>. Biomedical Reports, 23, 114. https://doi.org/10.3892/br.2025.1992
MLA
Nakao, K., Matsuo, T., Shimaoka, I., Hara, K."Modifying immune cells using mouse bone marrow‑derived cell exosomes during administration of heat‑killed lactic acid bacterium <em>Enterococcus faecalis</em>". Biomedical Reports 23.1 (2025): 114.
Chicago
Nakao, K., Matsuo, T., Shimaoka, I., Hara, K."Modifying immune cells using mouse bone marrow‑derived cell exosomes during administration of heat‑killed lactic acid bacterium <em>Enterococcus faecalis</em>". Biomedical Reports 23, no. 1 (2025): 114. https://doi.org/10.3892/br.2025.1992
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team