RRC ID 21421
Author Jounai K, Ikado K, Sugimura T, Ano Y, Braun J, Fujiwara D.
Title Spherical lactic acid bacteria activate plasmacytoid dendritic cells immunomodulatory function via TLR9-dependent crosstalk with myeloid dendritic cells.
Journal PLoS ONE
Abstract 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.
Volume 7(4)
Pages e32588
Published 2012
DOI 10.1371/journal.pone.0032588
PII PONE-D-11-21307
PMID 22505996
PMC PMC3323594
MeSH Animals Bone Marrow / immunology Bone Marrow / metabolism Cell Communication / immunology Cells, Cultured Coculture Techniques Dendritic Cells / immunology Dendritic Cells / metabolism Dendritic Cells / microbiology* Female Immunologic Factors / immunology Immunologic Factors / metabolism Interferon-alpha / immunology Interferon-alpha / metabolism Lactic Acid / metabolism Lactococcus lactis / immunology Lactococcus lactis / isolation & purification Lactococcus lactis / metabolism* Leuconostoc / immunology Leuconostoc / isolation & purification Leuconostoc / metabolism* Mice Mice, Inbred C57BL Myeloid Cells / immunology Myeloid Cells / metabolism Myeloid Cells / microbiology* Myeloid Differentiation Factor 88 / immunology Myeloid Differentiation Factor 88 / metabolism Pediococcus / immunology Pediococcus / isolation & purification Pediococcus / metabolism* Streptococcus / immunology Streptococcus / isolation & purification Streptococcus / metabolism* T-Lymphocytes, Regulatory / immunology T-Lymphocytes, Regulatory / metabolism Toll-Like Receptor 9 / immunology Toll-Like Receptor 9 / metabolism*
IF 2.766
Times Cited 21
General Microbes JCM 1180 JCM 5805 JCM 5886 JCM 11040 JCM 16167 JCM 20101