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Spherical Lactic Acid Bacteria Activate Plasmacytoid Dendritic Cells Immunomodulatory Function via TLR9-Dependent Crosstalk with Myeloid Dendritic Cells
Open accessAbstract
Plasmacytoid dendritic cells (pDC) are a specialized sensor of viral and bacterial nucleic acids and a major producer of IFN-α that promotes host defense by priming both innate and acquired immune responses. Although synthetic Toll-like receptor (TLR) ligands, pathogenic bacteria and viruses activate pDC, there is limited investigation of non-pathogenic microbiota that are in wide industrial dietary use, such as lactic acid bacteria (LAB). In this study, we screened for LAB strains, which induce pDC activation and IFN-α production using murine bone marrow (BM)-derived Flt-3L induced dendritic cell culture. Microbial strains with such activity on pDC were absent in a diversity of bacillary strains, but were observed in certain spherical species (Lactococcus, Leuconostoc, Streptococcus and Pediococcus), which was correlated with their capacity for uptake by pDC. Detailed study of Lactococcus lactis subsp. lactis JCM5805 and JCM20101 revealed that the major type I and type III interferons were induced (IFN-α, -β, and λ). IFN-α induction was TLR9 and MyD88-dependent; a slight impairment was also observed in TLR4(-/-) cells. While these responses occurred with purified pDC, IFN-α production was synergistic upon co-culture with myeloid dendritic cells (mDC), an interaction that required direct mDC-pDC contact. L. lactis strains also stimulated expression of immunoregulatory receptors on pDC (ICOS-L and PD-L1), and accordingly augmented pDC induction of CD4(+)CD25(+)FoxP3(+) Treg compared to the Lactobacillus strain. Oral administration of L. lactis JCM5805 induced significant activation of pDC resident in the intestinal draining mesenteric lymph nodes, but not in a remote lymphoid site (spleen). Taken together, certain non-pathogenic spherical LAB in wide dietary use has potent and diverse immunomodulatory effects on pDC potentially relevant to anti-viral immunity and chronic inflammatory disease.
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“phagocytosis of the strain Lactococcus lactis JCM 5805 by pDCs significantly stimulated IFN production via TLR9/MyD88 signaling (Jounai et al., 2012).”
From Viral Infections, the Microbiome, and Probiotics (2021) · cites this paper as Jounai et al., 2012
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Metadata
- Authors
- Jounai, K., Ikado, K., Sugimura, T., Ano, Y., Braun, J., & Fujiwara, D.
- Affiliations
- Kirin (Japan) (JP)
- University of California, Los Angeles (US)
- Corresponding author
- Fujiwara, Daisuke
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2012-04-10
- Volume
- 7
- Issue
- 4
- Pages
- e32588
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC3323594
- OpenAlex
- W2062007417
- Cited by
- 133
- References
- 54
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 12 · 2023: 15 · 2022: 11 · 2021: 11 · 2020: 7 · 2019: 7 · 2018: 12 · 2017: 9 · 2016: 8 · 2015: 10 · 2014: 5 · 2013: 6 · 2012: 1
- FWCI
- 3.07
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- National Institutes of Health (1ul1rr033176-01, UL1TR000124)
- National Institute of Allergy and Infectious Diseases (R01AI078885)
- National Center for Research Resources (UL1-RR-033176)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- lactic acid bacteria, plasmacytoid dendritic cells, myeloid dendritic cells, TLR9, MyD88, interferon-alpha, Lactococcus lactis, type I interferon, interferon lambda, TLR4, ICOSL, PD-L1, regulatory T cells, oral administration, mesenteric lymph nodes, immunomodulation, probiotics, antiviral immunity
- MeSH terms
- Animals, Bone Marrow, Cell Communication, Cells, Cultured, Dendritic Cells, Female, Immunologic Factors, Leuconostoc, Mice, Inbred C57BL, Pediococcus, Streptococcus, Lactococcus lactis, Interferon-alpha, Coculture Techniques, Lactic Acid, Myeloid Cells, T-Lymphocytes, Regulatory, Toll-Like Receptor 9, Mice, Myeloid Differentiation Factor 88
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