Academic Reports and External Announcements

Clinical trial papers

  • Effects of Ingesting Food Containing Heat-Killed Lactococcus lactis Strain Plasma on Fatigue and Immune-Related Indices after High Training Load: A Randomized, Double-Blind, Placebo-Controlled, and Parallel-Group Study

    Authors: Komano Y, Fukao K, Shimada K, Naito H, Ishihara Y, Fujii T, Kokubo T and Daida H.

    Nutrients 2023, 15, 1754.

    Focus:
    Male students in an athletic club ingested capsules containing 100 billion heated dead L. lactis Plasma or placebo capsules for 14 days. During the intake period, the subjects were made to continue high-intensity exercise according to the exercise team's practice regimen, and on day 15, they were subjected to 2 hours of bicycle exercise. Blood pDC activation was significantly increased in the L. lactis Plasma intake group compared to the placebo intake group during the intake period. In addition, the cumulative number of subjective onsets of fatigue symptoms decreased significantly. In addition, the autonomic nervous system fatigue index (LF/HF) was significantly reduced after bicycle exercise.

  • Efficacy of Lactococcus lactis strain plasma (LC-Plasma) in easing symptoms in patients with mild coronavirus disease (COVID-19): protocol for an exploratory, multicenter, double-blinded, randomized controlled trial (PLATEAU study)

    Authors: Yamamoto K, Hosogaya N, Inoue T, Jounai K, Tsuji R, Fujiwara D, Yanagihara K, Izumikawa K, Mukae H.

    BMJ Open 2022;12:e061172.
    doi:10.1136/bmjopen-2022-061172

    Focus:
    An exploratory multicenter trial (double-blind: placebo-controlled randomized trial) was designed to investigate whether oral intake of L. lactis Plasma could help alleviate or prevent the symptoms of COVID-19. The number of subjects scheduled to be enrolled is 100 (50 subjects x 2 groups). The primary evaluation item is change in subjective symptoms as measured by severity scores, and secondary evaluation items include amount of novel coronavirus, pDC activation markers, novel coronavirus-specific antibodies, and cytokines in blood.

  • Impact of Infectious Disease after Lactococcus lactis Strain Plasma Intake in Vietnamese Schoolchildren: A Randomized, Placebo-Controlled, Double-Blind Study

    Authors: Nghiem Nguyet Thu, Truong Tuyet Mai, Tran Thi Thu Trang, Nguyen Anh Tuan, Tran Chau Quyen, Nguyen Lien Hanh, Nguyen Huu Hoan, Bui Thi Huong Lan, Phung Thi Hau, Ha Huy Tue, Truong Viet Dung, Ryohei Tsuji, Yuta Watanabe, Naoki Yamamoto and Osamu Kanauchi

    Nutrients 2022, 14, 552.

    Focus:
    Healthy elementary school children in Ninh Binh Province, Vietnam ingested a beverage containing 100 billion heated dead L. lactis Plasma or a placebo beverage for 8 weeks. The cumulative number of days with fever during the intake period was significantly reduced in the group that ingested L. lactis Plasma. The cumulative number of days absent from school due to upper respiratory infection or gastroenteritis was also significantly reduced.

  • Lactococcus lactis Strain Plasma Intake Suppresses the Incidence of Dengue Fever-like Symptoms in Healthy Malaysians: A Randomized, Double-Blind, Placebo-Controlled Trial

    Authors: Khor C, Tsuji R, Lee H, Nor'e S, Sahimin N, Azman A, Tiong V, Hasandarvish P, Teoh B,C Soh Y, Chai J, Kokubo T, Kanauchi O, Yamamoto N, AbuBakar S

    Nutrients. 2021 Dec 16;13(12):4507.

    Focus:
    Healthy adult men and women living in a highly dengue-infected area near Kuala Lumpur, the capital of Malaysia, ingested tablets containing 100 billion heated dead L. lactis Plasma or placebo tablets for 8 weeks. There was no difference in the rate of infection with dengue virus, but there was a significant decrease in the cumulative number of subjective symptoms of dengue-like illness and flu/cold-like illness during the period of L. lactis Plasma intake.

  • Effects of Heat-Killed Lactococcus lactis Strain Plasma on Skin Homeostasis-Related Genes and the Skin Microbiome among Healthy Adults: A Randomized Controlled Double-Blind Study

    Authors: Fujii T, Fujitomo T, Tsuji R, Kubo R, Kato Y and Kanauchi O

    Microorganisms.9, 2029,2021

    Focus:
    FHealthy adult male and female subjects ingested capsules containing 100 billion heated dead L. lactis Plasma or placebo capsules for 8 weeks. Analysis of the skin microbiome by next-generation sequencing suggested that the L. lactis Plasma intake group may have maintained their skin microbiome. Furthermore, quantitative PCR analysis revealed that the expression of several tight junction genes and antimicrobial peptide genes was significantly increased in the L. lactis Plasma intake group.

  • Effect of Lactococcus lactis Strain Plasma on HHV-6 and HHV-7 Shedding in Saliva: A Prospective Observational Study.

    Authors: Miura H, Ihira M, Kozawa K, Kawamura Y, Higashimoto Y, Hattori F and Yoshikawa T

    Microorganisms.9, 1683,2021

    Focus:
    Human herpesvirus HHV-6 reactivates in salivary glands in response to various host stresses. Healthy adult male and female subjects ingested granules containing 100 billion heated dead L. lactis Plasma for 6 weeks. In the intake group under 40 years of age, comparison of before and after the L. lactis Plasma intake period showed that the amount of HHV-6 DNA detected was significantly lowered.

  • The Effects of dietary supplementation of Lactococcus lactis strain Plasma on Skin Microbiome and Skin conditions in Healthy Subjects-A Randomized, Double-Blind, Placebo-Controlled Trial

    Authors: Tsuji R, Yazawa K, Kokubo T, Nakamura Y, and Kanauchi O.

    Microorganisms. 9, 563, 2021.

    Focus:
    Healthy adult male and female subjects ingested capsules containing 100 billion heated dead L. lactis Plasma or placebo capsules for 8 weeks. The L. lactis Plasma intake group showed an inhibition of the decrease of Staphylococcus epidermidis on the skin, suggesting an inhibition of the proliferation of acne bacteria. In addition, the expression of antimicrobial peptide genes was increased. Clinical scores of skin condition improved in the L. lactis Plasma intake group.

  • Lactococcus lactis Strain Plasma Improves Subjective Physical State and Presenteeism:
    A Randomized, Open-label Crossover Study Among Healthy Office Workers.

    Authors: Kokubo T, Wakai S, Fujiwara D, Kanauchi O, Jounai K, Ichikawa H, Takuma M, Kanaya Y, and Shiraoka R

    Prev Nutr Food Sci. 25(2):140-145,2020.

    Focus:
    Male and female office workers were randomly divided into two groups: one group tested an L. lactis Plasma yogurt drink in the order of an intake and then non-intake period and the other group tested a non-intake and then intake period. Each period was set at 4 weeks, with a 4-week washout period in between. Absolute Presenteeism on the World Health Organization's Health and work Performance Questionnaire (HPQ) and Vitality on the Profile of Mood States (POMS) test were significantly improved during the L. lactis Plasma intake period compared to the non-intake period. In addition, the number of onsets of subjective symptoms of physical state, cough/sore throat, runny/stuffy nose, and fatigue improved significantly.

  • Efficacy of heat-killed Lactococcus lactis JCM 5805 on immunity and fatigue during consecutive high intensity exercise in male athletes: a randomized, placebo-controlled, double-blinded trial

    Authors: Komano Y, Shimada K, Naito H, Fukao K, Ishihara Y, Fujii T, Kokubo T, Daida H.

    J Int Soc Sports Nutr. 15: 39,2018.

    Focus:
    Male students who belonged to an athletic club were subject to intake of capsules containing 100 billion heated dead L. lactis Plasma or placebo capsules were ingested for 13 days. During the intake period, the subjects were made to continue high-intensity exercise according to the exercise team's practice regimen. Blood pDC activation was significantly increased in the L. lactis Plasma intake group compared to the placebo intake group during the intake period. In addition, the cumulative number of subjective symptoms such as sneezing and runny nose decreased significantly. Also, the cumulative number of days of subjective symptoms of fatigue decreased significantly.

  • Safety evaluation of excessive Intake of Lactococcus lactis subsp. lactis JCM 5805: a randomized, double-blind, placebo-controlled, parallel-group trial.

    Authors: Kato Y, Kanayama M, Yanai S, Nozawa H, Kanauchi O, Suzuki S.

    Food Nutr Sci. 9: 403-419,2018.

    Focus:
    Excess-intake safety testing was conducted in which healthy adult men and women ingested capsules containing 500 billion heated dead L. lactis Plasma or placebo capsules for 4 weeks. No clinically problematic findings or adverse effects were observed in the safety evaluation.

  • Effects of heat-killed Lactococcus lactis subsp. lactis JCM 5805 on mucosal and systemic immune parameters, and antiviral reactions to influenza virus in healthy adults; a randomized controlled double-blind study.

    Authors: Fujii T,Jounai K, Horie A, Takahashi H, Suzuki H, Ohshio K, Fujiwara D, Yamamoto N.

    J Func Food. 35: 513-521,2017.

    Focus:
    Healthy adult male and female subjects ingested capsules containing 100 billion heated dead L. lactis Plasma or placebo capsules for 4 weeks. The L. lactis Plasma intake group showed a significant decrease in the number of sore throat occurrences during the intake period compared to the placebo intake group. In addition, salivary IgA secretion was significantly increased. The results of evaluation of the reactivity of peripheral blood mononuclear cells collected from subjects with inactivated influenza A viruses (H1N1 and h4N2) showed that gene expression of the antiviral factors ISG-15, Irf7, and Mx-1 was significantly increased in the L. lactis Plasma intake group, especially in subjects who had received the influenza vaccine.

  • Preventive effect of Lactococcus lactis subsp. lactis JCM 5805 yogurt intake on influenza infection among schoolchildren.

    Authors: Sakata K, Sasaki Y, Jounai K, Fujii T, Fujiwara D.

    Health, 9: 756-762, 2017.

    Focus:
    L. lactis Plasma yogurt drinks were distributed to all elementary and junior high schools in the town of Shizukuishi, Iwate Prefecture, 3 times a week during lunch time for 25 days in winter. Compared to elementary and junior high school students in the adjacent Town A, where the influenza season that year was similar to that of the town of Shizukuishi, the rate of absenteeism due to influenza was lower in Shizukuishi.

  • Lactococcus lactis JCM 5805 activates anti-viral immunity and reduces symptoms of common cold and influenza in healthy adults in a randomized controlled trial.

    Authors: Shibata T, Kanayama M, Haida M, Fujimoto S, Oroguchi T, Sata K, Mita N, Kutsuzawa T, Ikeuchi M, Kondo M, Naito K, Tsuda M, Nishizaki Y, Ishii N.

    J Func Food. 24: 492-500,2016.

    Focus:
    Healthy adult male and female subjects ingested capsules containing 100 billion heated dead L. lactis Plasma or placebo capsules for 12 weeks. The L. lactis Plasma intake group showed a significant decrease in the number of occurrences of subjective symptoms of sore throat and cough during the intake period compared to the placebo intake group. In addition, the gene expression levels of antiviral factors in peripheral blood mononuclear cells collected from the subjects were evaluated, and the expression of IFN-α was significantly increased in the L. lactis Plasma intake group.

  • Study of safety of beverages containing Lactococcus lactis subsp. lactis JCM 5805 and indigestible dextrins during long-term intake and excess intake -A placebo-controlled, randomized, double-blind, parallel-group study-

    Authors: Kentaro Tanaka, Hiroaki Suzuki, Masaya Kanayama, Toshio Fujii, Daisuke Fujiwara, Hajime Nozawa, Haruhi Sugimura

    Pharmacology and Therapeutics (JPT) 43(12): 1711-27, 2015.

    Focus:
    A long-term intake safety study was conducted in which healthy male and female adults ingested a beverage containing 100 billion heated dead L. lactis Plasma for 12 weeks. Excess-intake safety testing was also conducted in which 3 bottles of the same beverage were consumed daily for 4 weeks. In both tests, no clinically problematic findings or adverse effects were observed in the safety evaluation.

  • Effects of ingesting a beverage containing Lactococcus lactis subsp. lactis JCM 5805 on antiviral immune response and maintenance of physical state -A placebo-controlled, randomized, double-blind, parallel-group study-

    Authors: Hiroaki Suzuki, Masaya Kanayama, Toshio Fujii, Daisuke Fujiwara, Haruhi Sugimura

    Pharmacology and Therapeutics (JPT) 43(10): 1465-27, 2015.

    Focus:
    Healthy adult male and female subjects ingested a beverage containing 100 billion heated dead L. lactis Plasma or placebo beverage for 8 weeks. Blood pDC activation was significantly increased in the L. lactis Plasma intake group compared to the placebo intake group. In addition, the number of subjective symptoms such as nasal discharge, arthritis pain, and chills that occurred during the period of L. lactis Plasma intake was significantly reduced. As a result of adding inactivated influenza A virus (H1N1) to peripheral blood mononuclear cells collected from subjects and evaluating their reactivity, the gene expression of the antiviral factor ISG-15 was significantly increased in the L. lactis Plasma intake group.

  • Effects of oral intake of plasmacytoid dendritic cells-stimulative lactic acid bacterial strain on pathogenesis of influenza-like illness and immunological response to influenza virus.

    Authors: Sugimura T, Takahashi H, Jounai K, Ohshio K, Kanayama M, Tazumi K, Tanihata Y, Miura Y, Fujiwara D, and Yamamoto N.

    Br J Nutr. 114:727-733,2015.

    Focus:
    Healthy adult men and women were given a yogurt drink fermented with L. lactis Plasma (containing 100 billion L. lactis Plasma) or a placebo drink for 10 weeks. The L. lactis Plasma group had half as many cases of influenza and colds and significantly fewer subjective symptoms during the intake period compared to the placebo group. In addition, the reactivity was evaluated by adding inactivated type A human influenza virus (H1N1) to peripheral blood mononuclear cells collected from the subjects, and the gene expression of the antiviral factor ISG-15 was significantly increased.

  • Immunomodulatory effect of Lactococcus lactis JCM 5805 on human plasmacytoid dendritic cells.

    Authors: Sugimura T, Jounai K, Ohshio K, Tanaka T, Suwa M, and Fujiwara D.

    Clin Immunol Vol 149: 509-518,2013.

    Focus:
    Healthy adult men and women were given a yogurt drink fermented with L. lactis Plasma (containing 100 billion L. lactis Plasma) or a placebo drink for 4 weeks. Blood pDC activation was significantly increased in the L. lactis Plasma intake group compared to the placebo intake group. In addition, the cumulative number of subjective influenza and cold-like symptoms during the period of L. lactis Plasma intake was significantly reduced.

Original Research Papers
(Non-Clinical)

  • Plasmacytoid dendritic cells stimulated with Lactococcus lactis strain Plasma produce soluble factors to suppress SARS-CoV-2 replication

    Authors: Ishii H, Jounai K, Tsuji R, Ohshio K, Kaneda D, Okazaki M, Harada S, Fujiwara D, Matano T

    Biochem Biophys Res Commun. 2023,662(25):26-30

    Focus:
    The effect of L. lactis Plasma on the inhibition of novel coronavirus proliferation was verified. The culture supernatant of pDCs supplemented with L. lactis Plasma was added to a normal kidney-derived cell line of African green monkey cells (Vero cells), which are susceptible to infection with the novel coronavirus, and cultured, and when they were infected with the novel coronavirus, the proliferation of the novel coronavirus in the Vero cells was inhibited. This effect was suggested to be the result of increased production of antiviral factors by pDC stimulation by L. lactis Plasma, which in turn resulted in increased expression of antiviral genes in Vero cells.

  • Plasmacytoid dendritic cell dysfunction caused by heat stress is improved by administration of Lactococcus lactis strain Plasma in mice.

    Authors: Sugimura T, Jounai K, Ohshio K, Fujiwara D.

    Biosci Biotec Biochem. 83(11):2140-2143, 2019.

    Focus:
    The effect of high temperature stress on immunity and the effectiveness of L. lactis Plasma were evaluated. When mice were kept under high temperature stress, pDC activation in the spleen was found to be reduced. Continued administration of L. lactis Plasma at this time was shown to improve the decreased pDC activation and IFN-α production capacity.

  • Staphylococcus aureus epicutaneous infection is suppressed by Lactococcus lactis strain Plasma via interleukin 17A elicitation.

    Authors: Tsuji R, Fujii T, Nakamura Y, Yazawa K, Kanauchi O.

    J Infect Dis. 220(5):892-901, 2019.

    Focus:
    The effects of L. lactis Plasma on the skin immune system and Staphylococcus aureus percutaneous infection were tested. Mice were infected with Staphylococcus aureus after continuous administration of L. lactis Plasma, and the counts of bacterial proliferation and skin condition were evaluated. Additionally, L. lactis Plasma was added to cultured lymphocytes and the secretion of IL-17A was evaluated. The results showed that the L. lactis Plasma group suppressed the proliferation of yellow staphylocytes and improved the inflammatory state of the skin compared to the control group. Studies in cultured cells suggest that this effect is mediated by induction of IL-17A production through activation of the TLR-9 pathway.

  • Characterization of genomic DNA of lactic acid bacteria for activation of plasmacytoid dendritic cells.

    Authors: Horie A, Tomita Y, Oshio K, Fujiwara D, Fujii T.

    BMC Microbiol. 19: 88, 2019.

    Focus:
    A random screening of the L. lactis Plasma genes was performed to verify the effect of genomic structure on the pDC activation effect. The results show that the GC content of the DNA fragments contributes to pDC activation and that the number of copies of the low GC region significantly affects the ability to activate pDCs as a lactic acid bacteria.

  • The effects of plasmacytoid dendritic cell-stimulative lactic acid bacteria, Lactococcus lactis strain Plasma, on exercise-induced fatigue and recovery via immunomodulatory action.

    Authors: Kokubo T, Komano Y, Tsuji R, Fujiwara D, Fujii T, Kanauchi O.

    Int J Sport Nutr Exerc Metab. 29(4):354-358, 2019.

    Focus:
    The effect of L. lactis Plasma on fatigue after exercise exertion was examined. Mice were continuously administered L. lactis Plasma, and spontaneous locomotor activity was evaluated after a short exercise load; the L. lactis Plasma group showed significantly less decline in spontaneous locomotor activity than the control group. This effect was not observed with other, common lactic acid bacteria. In addition, improvements were observed in the expression of muscle-degrading genes and in the amount of TGF-β, a type of fatigue indicator.

  • Administration of plasmacytoid dendritic cell-stimulative lactic acid bacteria is effective against dengue virus infection in mice

    Authors: Suzuki H, Tsuji R, Sugamata M, Yamamoto N, Yamamoto N, Kanauchi O.

    Int J Mol Med. 43:426-434, 2019.

    Focus:
    The effect of L. lactis Plasma on dengue virus infection was verified. Mice were infected with dengue virus after continuous administration of L. lactis Plasma; the amount of dengue virus in vivo was significantly lower in the L. lactis Plasma group than in the control group. Inflammatory reactions associated with dengue virus infection were also significantly suppressed in the L. lactis Plasma group. Non-infection experiments suggest that this effect is exerted by activation of pDCs by L. lactis Plasma via elevated expression of antiviral factors in peripheral tissues.

  • Induction of anti-viral genes mediated by humoral factors upon stimulation with Lactococcus lactis strain Plasma results in repression of dengue virus replication in vitro.

    Authors: Tsuji R, Yamamoto N, Yamada S, Fujii T, Yamamoto N, Kanauchi O.

    Antiviral Res. 160:101-108, 2018.

    Focus:
    The effect of L. lactis Plasma on dengue virus proliferation was tested. Liquid factors of bone marrow-derived dendritic cells obtained by stimulation with L. lactis Plasma were added to HepG2 cells, which inhibited dengue virus proliferation in HepG2 cells. This effect was exerted via type I interferon, and dengue virus proliferation was found to be inhibited regardless of serotype. Furthermore, this effect was not observed in other, common lactic acid bacteria and was thought to be characteristic of L. lactis Plasma.

  • Administration of plasmacytoid dendritic cell-stimulative lactic acid bacteria enhances antigen-specific immune responses

    Authors: Suzuki H, Jounai K, Ohshio K, Fujii T, Fujiwara D.

    Biochem Biophys Res Commun. 503:1315-1321,2018.

    Focus:
    The effect of L. lactis Plasma on antigen-specific immune responses was examined. Reaction of L. lactis Plasma with dendritic cells including pDCs resulted in a significant increase in the expression of MHC class I and II as well as CD80 and 86 on the surface of dendritic cells and antigen-specific T cell reactivity. Furthermore, continuous administration of L. lactis Plasma to mice promoted antigen-specific immune responses and the Th1 responses involved. These results suggest that L. lactis Plasma promotes antigen-specific immune responses via activation of dendritic cells including pDCs.

  • Long-term administration of pDC stimulative lactic acid bacteria, Lactococcus lactis strain Plasma, prevents immune-senescence and decelerates individual senescence.

    Authors: Tsuji R, Komano Y, Ohshio K, Ishii N, Kanauchi O.

    Exp Gerontol. 30;111:10-16,2018.

    Focus:
    The anti-aging effects of long-term intake of L. lactis Plasma were tested using SAMP1 and SAMP10 mice models with accelerated aging. The result was that in the SAMP1 mice, an immunosenescence suppression effect by promotion of IFN-α production and an increased ratio of naive T cells was observed in the L. lactis Plasma group. Also, in the SAMP10 mice, suppression of the age-related skin thinning phenomenon and increased expression of tight junction genes were observed. In addition, a significant reduction in aging scores was observed.

  • Long-term administration of pDC-stimulative Lactococcus lactis strain decelerates senescence and prolongs the lifespan of mice.

    Authors: Sugimura T, Jounai K, Ohshio K, Suzuki H, Kirisako T, Sugihara Y, Fujiwara D.

    Int Immunopharmacol. 58: 166-172,2018.

    Focus:
    Age-related decline in immune function has been shown to promote aging traits. The anti-aging effects of lifetime consumption of L. lactis Plasma were examined using the SAMP6 mouse model with accelerated aging. The results showed that the L. lactis Plasma group had a significantly longer life span than the control group, at 82 weeks. Furthermore, a significant decrease in the aging score, consisting of the sum of appearance and behavior scores, was found to occur in the L. lactis Plasma group compared to the control group. Dissection findings at 82 weeks showed a significant decrease in the hepatocyte abnormal proliferation foci and a trend toward a decreased frequency of abnormal findings in the liver and lungs in the L. lactis Plasma group. Epidermal cell thickness and muscle mass were maintained significantly higher in the L. lactis Plasma group. The pDC activation was significantly higher in the L. lactis Plasma group. These results indicate that L. lactis Plasma exerts anti-aging and lifespan-extending effects by maintaining pDC-mediated immunity.

  • Enhancement of immunomodulative effect of lactic acid bacteria on plasmacytoid dendritic cells with sucrose palmitate.

    Authors: Kanayama M, Kato Y, Tsuji T, Konoeda Y, Hashimoto A, Kanauchi O, Fujii T, Fujiwara D.

    Sci Rep. 8: 3147,2018.

    Focus:
    We found that L. lactis Plasma treated with an emulsifier based on sucrose fatty acid esters dramatically increased activation in vitro. This was suggested to be due to an increased amount of L. lactis Plasma being taken in by pDCs. Emulsifier-treated L. lactis Plasma increased local antiviral gene expression in the lungs more than untreated L. lactis Plasma when administered orally. These results indicate that emulsifier treatment with sucrose fatty acid esters as the main ingredient enhances the effect of the L. lactis Plasma.

  • Administration of Lactococcus lactis strain Plasma induces maturation of plasmacytoid dendritic cells and protection from rotavirus infection in suckling mice.

    Authors: Jounai K, Sugimura T, Morita Y, Ohsio K, Fujiwara D.

    Int Immunopharmacol. 56: 205-211,2018.

    Focus:
    In an experimental system in which rotavirus was transmitted to 7-day-old mice, the L. lactis Plasma group showed improvement over the placebo group in weight suppression, fecal score, and viral load. To elucidate the mechanism, we used 7-day-old uninfected mice, and administration of L. lactis Plasma caused maturation of pDCs and an increase in the pDC ratio in the mucosal lamina propria of the small intestine. Furthermore, the expression levels of various IFN-inducible antiviral factors in small intestinal epithelial cells were increased. These results suggest that administration of L. lactis Plasma exerts a protective effect against rotavirus infection by immunostimulation of the local intestinal tract.

  • Lactococcus lactis subsp. lactis JCM 5805 activates natural killer cells via dendritic cells.

    Authors: Suzuki H, Ohshio K, Fujiwara D.

    Biosci Biotec Biochem. 80: 798-800,2016.

    Focus:
    Addition of L. lactis Plasma to mouse spleen cells caused activation of NK cells. Mechanism of action analysis revealed that L. lactis Plasma does not directly stimulate and activate NK cells, but rather via dendritic cells. Activation of NK cells in the spleen was also observed when L. lactis Plasma was orally administered to mice for 2 weeks.

  • Draft genome sequence of Lactococcus lactis subsp. lactis JCM 5805T, a strain that induces plasmacytoid dendritic cell activation.

    Authors: Fujii T, Tomita Y, Ikushima S, Horie A, Fujiwara D.

    Genome Announc 3(2) : e00113-15,2015.

    Focus:
    Genomic information analysis of L. lactis Plasma was performed. The genome size of L. lactis Plasma was 2.55 Mb with a GC content of 35.2%. Draft genome sequences and gene annotations were published in the DDBJ database.

  • Oral administration of Lactococcus lactis subsp. lactis JCM 5805 enhances lung immune response resulting in protection from murine parainfluenza virus infection.

    Authors: Jounai K, Sugimura T, Ohshio K, and Fujiwara D.

    PLoS One 10(3): e0119055,2015.

    Focus:
    When mice were infected with parainfluenza virus after oral administration of L. lactis Plasma for 2 weeks, all individuals in the control group died within 10 days, whereas 70% of the L. lactis Plasma group survived. At that time, the L. lactis Plasma group showed a significant reduction in pneumonia symptoms. The mechanism of action analysis showed that oral administration of L. lactis Plasma caused activation of pDCs and increased IFN production in Peyer's patches in the intestinal tract and increased expression of various antiviral factors in the lung tissue.

  • Spherical lactic acid bacteria activate plasmacytoid dendritic cells immunomodulatory function via TLR9-dependent crosstalk with myeloid dendritic cells.

    Authors: Jounai K, Ikado K, Sugimura T, Ano Y, Braun J, and Fujiwara D.

    PLoS One 7(4): e32588,2012.

    Focus:
    For the first time, lactic acid bacteria were discovered that activate plasmacytoid dendritic cells, which play an important role in viral infection defense, and induce IFN-α production. All activated strains, including L. lactis Plasma, were classified as lactococci, and lactic acid bacteria of the genus Lactobacillus, which are widely used in industry, could not be activated. Analysis of the mechanism of action revealed that TLR9, which is expressed within pDC cells, is stimulated by DNA in lactic acid bacteria. Oral administration of L. lactis Plasma to mice for 2 weeks also resulted in activation of pDCs and mDCs in mesenteric lymph nodes.