---
title: "OLL1073R-1 and OLS3059 activate dendritic cells and boost anti-viral responses"
id: "plos-one-6-activation-of-conventional-and-plasmacytoid-dendritic-cells-and-enhancement-of"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-6-activation-of-conventional-and-plasmacytoid-dendritic-cells-and-enhancement-of"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545"
published_at: "2026-09-29T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# OLL1073R-1 and OLS3059 activate dendritic cells and boost anti-viral responses
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/plos-one-6-activation-of-conventional-and-plasmacytoid-dendritic-cells-and-enhancement-of
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545)
- **Published At:** 2026-09-29T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- Dendritic cells (DCs) comprise **conventional DCs (cDCs)** and **plasmacytoid DCs (pDCs)**; both subsets are central to antiviral immunity through antigen presentation and type I interferon production, respectively. - Prior clinical and animal studies linked consumption of yogurt fermented with Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1 and Streptococcus thermophilus OLS3059 to reduced viral infection and improved respiratory symptoms. - This study tested whether OLL1073R-1 and OLS3059 directly activate human cDCs and pDCs and whether that activation supports anti-viral immune responses. - Using human PBMCs, both heat-treated OLL1073R-1 and OLS3059 increased activation markers (CD86, CD40, HLA-DR) on **pDCs** and raised IL-12 expression in **cDCs**, indicating activation of both subsets. - Isolated cDCs and pDCs derived from CD34(+) progenitors were directly activated by OLL1073R-1, with increased CD86, CD40 and HLA-DR expression, demonstrating effects independent of other immune cells. - mRNA-seq after 6 h stimulation identified hundreds of differentially expressed genes in each DC subset; pathway enrichment implicated immune-related processes upregulated by OLL1073R-1 in both cDCs and pDCs. - Functional assays on PBMCs depleted of cDCs or pDCs showed that both subsets were required for **type I interferon** production in response to OLL1073R-1, while cDCs (not pDCs) were necessary for enhanced effector-memory CD4+ T cell responses to influenza antigen and for IL-12–dependent effects. - Phagocytosis assays and cytokine measurements supported uptake of OLL1073R-1 by DCs and downstream cytokine release (IL-12, IFN-α2a, IFN-β). - Authors conclude the anti-viral immune effects linked to consumption of this yogurt are mediated by both **OLL1073R-1** and **OLS3059** via activation of **cDCs** and **pDCs**. - Funding and competing interests: study funded by Meiji Holdings Co., Ltd.; authors are employees of Meiji Holdings. No other funding; all data reported are within the manuscript and supplements.
## Clinical Analysis & Structured Key Points
[ Skip to main content ](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#main-content) Advertisement * [plos.org](https://plos.org/) * [Create account](https://community.plos.org/registration/new) * [Sign in](https://journals.plos.org/user/secure/login?page=%2Fplosone%2Farticle%3Fid%3D10.1371%2Fjournal.pone.0359545) * * About * Browse * Publish * [](https://journals.plos.org/plosone/ "PLOS One") * Search [advanced search](https://journals.plos.org/plosone/search) * [Browse Topics](https://journals.plos.org/plosone/subjectAreaBrowse) Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click [here](https://github.com/PLOS/plos-thesaurus/blob/master/README.md "Link opens in new window"). [](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545) [](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545) * 0 [Save](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0359545#savedHeader) [Total Mendeley and Citeulike bookmarks.](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0359545#savedHeader) * 0 [Citation](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0359545#citedHeader) [Paper's citation count computed by Dimensions.](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0359545#citedHeader) * 10 [View](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0359545#viewedHeader) [PLOS views and downloads.](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0359545#viewedHeader) * 0 [Share](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0359545#discussedHeader) [Sum of Facebook, Twitter, Reddit and Wikipedia activity.](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0359545#discussedHeader) Open Access Peer-reviewed Research Article # Activation of conventional and plasmacytoid dendritic cells and enhancement of anti-viral immune responses by _Lactobacillus delbrueckii_ subsp. _bulgaricus_ OLL1073R-1 and _Streptococcus thermophilus_ OLS3059 * Hiroki Kono , Roles Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Resources, Software, Validation, Visualization, Writing – original draft * E-mail: hiroki.kouno@meiji.com Affiliation Wellness Science Labs, Meiji Holdings Co., Ltd., Hachioji, Tokyo, Japan [ ![ORCID logo](https://journals.plos.org/resource/img/orcid_16x16.png) https://orcid.org/0009-0005-0354-0234 ](https://orcid.org/0009-0005-0354-0234 "ORCID Registry") ⨯ * Toshihiro Sashihara Roles Project administration, Supervision, Writing – review & editing Affiliation Wellness Science Labs, Meiji Holdings Co., Ltd., Hachioji, Tokyo, Japan ⨯ # Activation of conventional and plasmacytoid dendritic cells and enhancement of anti-viral immune responses by _Lactobacillus delbrueckii_ subsp. _bulgaricus_ OLL1073R-1 and _Streptococcus thermophilus_ OLS3059 * Hiroki Kono, * Toshihiro Sashihara ![PLOS](https://journals.plos.org/resource/img/logo-plos-full-color.svg) x * Published: September 29, 2026 * * [Article](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545) * [Authors](https://journals.plos.org/plosone/article/authors?id=10.1371/journal.pone.0359545) * [Metrics](https://journals.plos.org/plosone/article/metrics?id=10.1371/journal.pone.0359545) * [Comments](https://journals.plos.org/plosone/article/comments?id=10.1371/journal.pone.0359545) * [Media Coverage](http://plos.altmetric.com/details/doi/10.1371/journal.pone.0359545) * [Abstract](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#abstract0) * [Introduction](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#sec001) * [Materials and methods](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#sec002) * [Result](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#sec012) * [Discussion](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#sec019) * [Conclusion](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#sec020) * [Supporting information](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#sec021) * [Acknowledgments](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#ack) * [References](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#references) * [Reader Comments](https://journals.plos.org/plosone/article/comments?id=10.1371/journal.pone.0359545) * [Figures](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545) ## Abstract Dendritic cells are classified into conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs), both of which play critical roles in anti-viral immune responses. Previous studies have reported that dairy consumption of yogurt fermented with _Lactobacillus delbrueckii_ subsp. _bulgaricus_ OLL1073R-1 and _Streptococcus thermophilus_ OLS3059 had the effect of inhibiting viral infections. Recent studies have shown that the activation of both cDCs and pDCs and the decrease of respiratory symptoms were induced by the consumption of this yogurt. However, the components responsible for these effects and the underlying mechanisms remain unclear. Since several reports have shown that cDCs and pDCs were activated by lactic acid bacteria, we hypothesized _L_. _bulgaricus_ OLL1073R-1 and _S. thermophilus_ OLS3059 induced anti-viral immune responses by activating cDCs and pDCs. Here we demonstrated that both _L_. _bulgaricus_ OLL1073R-1 and _S. thermophilus_ OLS3059 activate cDCs and pDCs in human peripheral blood mononuclear cells. We also showed that both cDCs and pDCs were necessary for type I interferon production, whereas cDCs, but not pDCs, were essential for enhancing effector memory CD4(+) T cell responses to viral antigens when stimulated by _L_. _bulgaricus_ OLL1073R-1. These findings indicate that anti-viral immune responses induced by consumption of this yogurt are mediated by both _L_. _bulgaricus_ OLL1073R-1 and _S. thermophilus_ OLS3059 through activation of cDCs and pDCs. ## Figures ![Fig 4](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0359545.g004) ![Fig 5](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0359545.g005) ![Fig 6](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0359545.g006) ![Fig 1](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0359545.g001) ![Fig 2](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0359545.g002) ![Fig 3](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0359545.g003) ![Fig 4](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0359545.g004) ![Fig 5](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0359545.g005) ![Fig 6](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0359545.g006) ![Fig 1](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0359545.g001) ![Fig 2](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0359545.g002) ![Fig 3](https://journals.plos.org/plosone/article/figure/image?size=inline&id=10.1371/journal.pone.0359545.g003) **Citation:** Kono H, Sashihara T (2026) Activation of conventional and plasmacytoid dendritic cells and enhancement of anti-viral immune responses by _Lactobacillus delbrueckii_ subsp. _bulgaricus_ OLL1073R-1 and _Streptococcus thermophilus_ OLS3059. PLoS One 21(9): e0359545. https://doi.org/10.1371/journal.pone.0359545 **Editor:** Masanori A. Murayama, Kansai Medical University: Kansai Ika Daigaku, Institute of Biomedical Science, JAPAN **Received:** March 25, 2026; **Accepted:** September 11, 2026; **Published:** September 29, 2026 **Copyright:** © 2026 Kono, Sashihara. This is an open access article distributed under the terms of the [Creative Commons Attribution License](http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. **Data Availability:** All relevant data are within the manuscript and its [Supporting Information](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#sec021) files. **Funding:** The author(s) received no specific funding for this work. **Competing interests:** Authors are employees of Meiji Holdings Co., Ltd., Japan. This study was funded by Meiji Holdings Co., Ltd., Japan. The authors declare no other competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials. ## Introduction Dendritic cells (DCs) are the central regulators of the immune system, bridging innate and adaptive immunity by recognizing pathogens through various receptors and inducing antigen-specific responses and immune memory [[1](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref001)]. Human DCs differentiate from CD34(+) hematopoietic progenitor cells into two major subsets: conventional dendritic cells (cDCs) and plasmacytoid dendritic cells (pDCs), which migrate into blood and peripheral tissues [[2](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref002),[3](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref003)]. cDCs are predominant DC subset and are responsible for activating T cells by antigen presentation or cytokine production [[3](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref003),[4](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref004)]. In contrast, pDCs are characterized by producing large amounts of type I interferons (IFNs) in response to pathogens [[3](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref003),[5](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref005)]. DCs have been reported to play an important role in the control of infectious diseases as well as in the pathogenesis of various immune diseases including autoimmune diseases, allergy, cancer [[6](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref006),[7](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref007)]. cDCs recognize viruses, bacteria and fungus through a variety of pattern recognition receptors such as Toll-like receptors (TLRs) [[8](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref008)]. pDCs highly express TLR7 and TLR9 which are known as intracellular receptors and recognize viral single-stranded RNA and CpG rich DNA [[8](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref008)]. Several reports have shown that experimental depletion of cDCs leads to increase pathogen burden and reduce survival rate during infection of viruses or bacteria [[9](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref009)–[12](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref012)]. Similarly, depletion of pDCs has been shown to impair antigen-specific antibody production during viral infections [[10](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref010)]. In humans, both cDCs and pDCs have been also reported to be related to induction of immune responses and clearance of pathogens during infections [[13](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref013),[14](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref014)]. Collectively, these findings suggest that the activation of cDCs and pDCs plays a critical role in suppressing infection of various viruses or bacteria. Several reports have shown that the consumption of probiotic drink containing lactic acid bacteria decrease the frequency of catching respiratory infectious diseases [[15](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref015)–[17](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref017)]. Our studies have shown that immunomodulatory effects such as activation of natural killer cells and improvement of respiratory symptoms were induced by the consumption of the yogurt fermented with _Lactobacillus delbrueckii_ subsp. _bulgaricus_ OLL1073R-1 (hereafter referred as OLL1073R-1) and _Streptococcus thermophilus_ OLS3059 (hereafter referred as OLS3059) [[18](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref018)–[22](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref022)]. We have also reported by using influenza infection mouse model that intake of this yogurt reduced viral load and improved survival rate [[23](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref023)]. We have shown in human study that influenza-reactive salivary immunoglobulin A (IgA) and serum IgG levels after influenza vaccination were increased by the consumption of this yogurt [[24](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref024)]. These findings collectively indicate that suppression of viral infection is mediated by the consumption of yogurt fermented with OLL1073R-1 and OLS3059. It has been reported that cDCs and pDCs are activated by several kinds of lactic acid bacteria _in vitro_ experiments [[25](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref025)–[28](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref028)]. Our recent human studies have shown that both activation of cDCs and pDCs and improvement of respiratory symptoms are induced by daily consumption of the yogurt [[20](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref020),[21](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref021)]. Based on these observations, we hypothesized that OLL1073R-1 and OLS3059 contained in the yogurt activated cDCs and pDCs and thereby enhanced anti-viral immune responses. In the present study, we used human peripheral blood mononuclear cells (PBMCs) to clarify whether cDCs and pDCs were activated by OLL1073R-1 and OLS3059 and determine how such activation contributes to anti-viral immune responses. Through this approach, we aimed to understand whether and how lactic acid bacteria induce anti-viral immune responses by acting on cDCs and pDCs. ## Materials and methods ### Preparation of lactic acid bacterial cells _L_. _bulgaricus_ OLL1073R-1, JCM 1002T, MH250033, MH250034 were cultured by using Difco™ Lactobacilli De Man-Rogosa-Sharpe (MRS) Broth (BD, New Jersey, USA) and _S. thermophilus_ OLS3059, JCM 17834T, MH260001, MH260002 were cultured by Difco™ M17 Broth (BD) at 37°C, anaerobic, state condition for 18 h after preculture of the cryopreserved stocks. Bacteria were washed twice by phosphate-buffered saline (PBS) and were heat-treated at 75°C for 1 h and were preserved at −80°C until used in following experiments. The number of bacteria was calculated by counting colonies on Difco™ Lactobacilli MRS Agar (BD) using bacteria suspension before heat-treated. Strains OLL1073R-1, MH250033, MH250034, OLS3059, MH260001 and MH260002 were obtained from Meiji Co., Ltd. (Tokyo, Japan) Strain JCM 1002T and JCM 17834T was purchased from Japan Collection of Microorganisms (Tsukuba, Japan). ### Stimulation of PBMCs with lactic acid bacteria Human PBMCs (Precision for Medicine, Bethesda, USA) were seeded at a concentration of 5 × 105 cells/well and cultured in 200 μL medium at 37°C, 5% CO2 with or without lactic acid bacteria at a concentration of 1 × 106 bacterial cells/mL for 24 h. Roswell park memorial institute (RPMI) 1640 Medium (Thermo Fisher Scientific, Massachusetts, USA) containing 10% fetal bovine serum (FBS) was used for incubation. Cells were stained by anti-human lineage cocktail 1 fluorescein isothiocyanate (FITC) (BD), anti-human leukocyte antigen (HLA) -DR allophycocyanin (APC) (BD), anti-CD11c brilliant violet (BV) 421 (BD), anti-CD123 BV510 (BD), anti-CD304 phycoerythrin (PE) (BD), anti-CD86 PE-Cyanine (Cy) ™7 (BD), anti-CD40 peridinin chlorophyll protein (PerCP) -Cy™5.5 (Biolegend, San Diego, USA), Fixable Viability Dye eFluor™ 780 (Thermo Fisher Scientific) after blocking with Human BD Fc Block™ (BD) and were fixed and permeated by BD Cytofix/Cytoperm™ Fixation/Permeabilization Kit (BD) and were analyzed CD86, HLA-DR, CD40 expression of cDCs or pDCs fraction by BD FACS Lyric™ (BD). When performing intracellular staining of IL-12, BD GolgiStop™ Protein Transport Inhibitor (BD) was added 2 h after cultivation of PBMCs with lactic acid bacteria when intracellular staining of interleukin (IL) −12 was performed. Cells were stained by anti-human lineage cocktail 1 FITC (BD), anti-HLA-DR APC (BD), anti-CD11c BV421 (BD), anti-CD123 BV510 (BD), anti-CD304 PE (BD), Fixable Viability Dye eFluor™ 780 (Thermo Fisher Scientific) after blocking and were fixed and permeated and were stained by anti-IL-12 PE (BD) and were analyzed IL-12 expression of cDCs fraction by BD FACS Lyric™ (BD). ### Differentiation of DCs and sorting of cDCs and pDCs fraction The differentiation from CD34(+) hematopoietic progenitor cells (HPCs) into cDCs and pDCs was performed according to previous study [[29](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0359545#pone.0359545.ref029)]. Human cord blood CD34(+) cells (Stemcell Technologies, Vancouver, Canada) were cultured at 37°C, 5% CO2 for 3 weeks by using X-VIVO15 medium (Lonza, Basel, Switzerland) with 10% FBS, 1% sodium pyruvate and 1% non-essential amino acids containing 20 ng/mL IL-3 (Thermo Fisher Scientific), 50 ng/mL thrombopoietin (TPO; Thermo Fisher Scientific) and 100 ng/mL Fms-like tyrosine kinase 3 ligand (Flt3-L; Thermo Fisher Scientific). Cells were stained by anti-human lineage cocktail 1 FITC (BD), anti-HLA-DR APC (BD), anti-CD11c BV421 (BD), anti-CD123 BV510 (BD), anti-CD304 PE (BD) after blocking and sorted cDCs and pDCs fractions by BD FACS Melody™ (BD). Sorted cDCs and pDCs fractions were defined as each “isolated cDCs” and “isolated pDCs”. ### Stimulation of isolated cDCs and pDCs with OLL1073R-1 Isolated cDCs and pDCs were each seeded at a concentration of 2 × 104 cells/well and 5 × 104 cells/well, respectively, and cultured in 200 μL medium at 37°C, 5% CO2 with or without OLL1073R-1 (1 × 106 bacterial cells/mL) for 6 h or 24 h. RNA samples from cells incubated for 6 h were extracted by Maxwell® RSC simplyRNA Cells Kit (Promega, Madison, USA) and were used for mRNA-seq and qPCR. Cells incubated for 24 h were stained by anti-CD86 PE-Cy™7 (BD), anti-CD40 PerCP-Cy™5.5 (Biolegend), Fixable Viability Dye eFluor™ 780 (Thermo Fisher Scientific) after blocking and were fixed and permeated by BD Cytofix/Cytoperm™ Fixation/Permeabilization Kit (BD) and were analyzed CD86, HLA-DR, CD40 expression of live cells by BD FACS Lyric™ (BD). Supernatants of cells incubated for 24 h were used for qu
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