Tadaomi Kawashima

Lactobacillus plantarum strain YU from fermented foods activates Th1 and protective immune responses.

Lactic acid bacteria (LAB) are known to have effects on immune function. From 203 strains of LAB isolated from fermented foods, we selected a beneficial strain, Lactobacillus plantarum strain YU (LpYU), which has high interleukin (IL)-12-inducing activity in mouse peritoneal macrophages. This activity of LpYU was partially mediated by Toll-like receptor (TLR) 2, but not TLR4 or TLR9. Oral administration of LpYU to ovalbumin (OVA)-immunized mice caused suppression of serum OVA-specific immunoglobulin E (IgE) levels, enhancing interferon (IFN)-γ production from spleen cells in response to OVA. Furthermore, LpYU enhanced natural killer cell activity in spleen cells and the production of IgA from Peyers patch cells. Because activation of Th1 immune responses and IgA production induce antiviral effects, we evaluated the inhibitory effects of LpYU against the influenza A virus (A/NWS/33, H1N1) (IFV). Oral administration of LpYU suppressed viral proliferation in the lungs and in bronchoalveolar lavage fluids (BALFs). Both levels of IFV-specific secretory IgA in BALF and feces and titers of IFV-specific neutralizing antibody in BALFs and sera were increased. These results indicate that LpYU has a protective effect against IFV replication. We conclude that this strain has a beneficial effect in activating Th1 immune responses and preventing viral infection.

A sulfated polysaccharide, fucoidan, enhances the immunomodulatory effects of lactic acid bacteria

Fucoidan, a sulfated polysaccharide contained in brown algae, has a variety of immunomodulatory effects, including antitumor and antiviral effects. On the other hand, lactic acid bacteria (LAB) also have immunomodulatory effects such as anti-allergic effects. In this study, we demonstrated that fucoidan enhances the probiotic effects of LAB on immune functions. By using Peyers patch cells and spleen cells in vitro, fucoidan amplified interferon (IFN)-γ production in response to a strain of LAB, Tetragenococcus halophilus KK221, and this activity was abolished by desulfation of fucoidan. Moreover, this IFN-γ response was abolished by interleukin (IL)-12 neutralization. These results indicate that fucoidan enhanced IL-12 production in response to KK221, resulting in promoting IFN-γ production. In an in vivo study, Th1/Th2 immunobalance was most improved by oral administration of both fucoidan and KK221 to ovalbumin-immunized mice. These findings suggest that fucoidan can enhance a variety of beneficial effects of LAB on immune functions.

A Marine Carotenoid, Fucoxanthin, Induces Regulatory T Cells and Inhibits Th17 Cell Differentiation in Vitro

Fucoxanthin is a non-provitamin A carotenoid contained in brown seaweeds. We found that it suppressed interleukin-17 secretion from CD4+ T cells under IL-17-producing T (Th17) cell development conditions. By evaluating T cell differentiation in vitro, fucoxanthin and its metabolite fucoxanthinol inhibited T cell differentiation into Th17 cells. This suggests that fucoxanthin can improve inflammatory diseases due to Th17 cells.

The molecular mechanism for activating IgA production by Pediococcus acidilactici K15 and the clinical impact in a randomized trial

IgA secretion at mucosal sites is important for host defence against pathogens as well as maintaining the symbiosis with microorganisms present in the small intestine that affect IgA production. In the present study, we tested the ability of 5 strains of lactic acid bacteria stimulating IgA production, being Pediococcus acidilactici K15 selected as the most effective on inducing this protective immunoglobulin. We found that this response was mainly induced via IL-10, as efficiently as IL-6, secreted by K15-stimulated dendritic cells. Furthermore, bacterial RNA was largely responsible for the induction of these cytokines; double-stranded RNA was a major causative molecule for IL-6 production whereas single-stranded RNA was critical factor for IL-10 production. In a randomized, double-blind, placebo-controlled clinical trial, ingestion of K15 significantly increased the secretory IgA (sIgA) concentration in saliva compared with the basal level observed before this intervention. These results indicate that functional lactic acid bacteria induce IL-6 and IL-10 production by dendritic cells, which contribute to upregulating the sIgA concentration at mucosal sites in humans.

Double-Stranded RNA Derived from Lactic Acid Bacteria Augments Th1 Immunity via Interferon-β from Human Dendritic Cells

Lactic acid bacteria (LAB) are one of the major commensal species in the small intestine and known for contributing to maintenance of protective immunity and immune homeostasis. However, currently there has been no evidence regarding the cellular mechanisms involved in the probiotic effects of LAB on human immune cells. Here, we demonstrated that LAB double-stranded RNA (dsRNA) triggered interferon-β (IFN-β) production by human dendritic cells (DCs), which activated IFN-γ-producing T cells. Interleukin-12 (IL-12) secretion from human DCs in response to LAB was abrogated by depletion of bacterial dsRNA, and was attenuated by neutralizing IFN-β, indicating LAB dsRNA primarily activated the IFN-β/IL-12 pathway. Moreover, the induction of IL-12 secretion from DCs by LAB was abolished by the inhibition of endosomal acidification, confirming the critical role of the endosomal digestion of LAB. In a coculture of human naïve CD4+ T cells and BDCA1+ DCs, DCs stimulated with LAB containing dsRNA induced IFN-γ-producing T cells. These results indicate that human DCs activated by LAB enhance Th1 immunity depending on IFN-β secretion in response to bacterial dsRNA.