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Antigen-specific immunoglobulin (Ig) A plays a major role in host defense against infections in gut mucosal tissue. Follicular helper T (Tfh) cells are located in germinal centers and promote IgA production via interactions with germinal center B cells. Several studies have demonstrated that some lactic acid bacteria (LAB) strains activate the host’s acquired immune system, inducing IgA secretion in the intestine. However, the precise molecular mechanisms underlying the effects of LAB on IgA production and Tfh cells are not fully resolved. Lactobacillus paracasei MCC1849 is a probiotic strain isolated from the intestine of a healthy adult. In this study, we investigated the effects of orally administered heat-killed MCC1849 on IgA production in the intestine and on Tfh cell induction in vivo. We found that orally administered MCC1849 induced antigen-specific IgA production in the small intestine, serum and lungs. We also observed that MCC1849 increased the proportion of IgA+ B cells and Tfh cells in Peyer’s patches (PPs). In addition, MCC1849 increased the gene expression of IL-12p40, IL-10, IL-21, STAT4 and Bcl-6 associated with Tfh cell differentiation. These results suggest that orally administered MCC1849 enhances antigen-specific IgA production and likely affects Tfh cell differentiation in PPs. [ABSTRACT FROM AUTHOR]

Food allergy is a serious problem for infants and young children. Induction of antigen-specific oral tolerance is one therapeutic strategy. Enhancement of oral tolerance induction by diet is a promising strategy to prevent food allergy in infants. Thus, in this study, we evaluate the effect of probiotic Lactobacillus gasseri OLL2809 (LG2809) on oral tolerance induction in a mouse model. The degree of oral tolerance induction was evaluated by measuring the proliferation and level of IL-2 production of splenic CD4+ T cells from DO11.10 mice fed ovalbumin (OVA) alone or OVA with LG2809. Oral administration of LG2809 significantly decreased the rate of proliferation and IL-2 production by CD4+ T cells from OVA-fed mice. LG2809 increased a ratio of CD4+ T-cell population, producing high levels of IL-10 and having strong suppressive activity. Moreover, LG2809 increased a ratio of plasmacytoid dendritic cells (pDCs) among the lamina propria (LP) in small intestine. When used as antigen presenting cells to naïve CD4+ T cells from DO11.10 mice, LP cells from BALB/c mice fed LG2809 induced higher IL-10 production and stronger suppressive activity than those from non-treated mice. These results suggest that oral administration of LG2809 increases the population of pDCs in the LP, resulting in the enhancement of oral tolerance induction by increasing the ratio of effector regulatory T cells. LG2809 could, therefore, act as a potent immunomodulator to prevent food allergies by promoting oral tolerance. [ABSTRACT FROM AUTHOR]

Inflamm-aging indicates the chronic inflammatory state resulting from increased secretion of proinflammatory cytokines and mediators such as IL-6 in the elderly. Our principle objective was to identify cell types that were affected with aging concerning IL-6 secretion in the murine model. We compared IL-6 production in spleen cells from both young and aged mice and isolated several types of cells from spleen and investigated IL-6 mRNA expression and protein production. IL-6 protein productions in cultured stromal cells from aged mice spleen were significantly high compared to young mice upon LPS stimulation. IL-6 mRNA expression level of freshly isolated stromal cells from aged mice was high compared to young mice. Furthermore, stromal cells of aged mice highly expressed IL-6 mRNA after LPS injection in vivo. These results suggest that stromal cells play a role in producing IL-6 in aged mice and imply that they contribute to the chronic inflammatory condition in the elderly. [ABSTRACT FROM AUTHOR]

The mucosal immune system provides the first line of defense against inhaled and ingested pathogenic microbacteria and viruses. This defense system, to a large extent, is mediated by the actions of secretory IgA. In this study, we screened 140 strains of lactic acid bacteria for induction of IgA production by murine Peyer’s patch cells. We selected one strain and named it Lactobacillus plantarum AYA. We found that L. plantarum AYA-induced production of IL-6 in Peyer’s patch dendritic cells, with this production promoting IgA+ B cells to differentiate into IgA-secreting plasma cells. We also observed that oral administration of L. plantarum AYA in mice caused an increase in IgA production in the small intestine and lung. This production of IgA correlated strongly with protective ability, with the treated mice surviving longer than the control mice after lethal influenza virus infection. Our data therefore reveals a novel immunoregulatory role of the L. plantarum AYA strain which enhances mucosal IgA production and provides protection against respiratory influenza virus infection. [ABSTRACT FROM AUTHOR]

As a kind of metabolically triggered inflammation, obesity influences the interplay between the central nervous system and the enteral environment. The present study showed that β-elemene, which is contained in various plant substances, had effects on recovering the changes in metabolites occurring in high-fat diet (HFD)-induced obese C57BL/6 male mice brains, especially in the prefrontal cortex (PFC) and hippocampus (HIP). β-elemene also partially reversed HFD-induced changes in the composition and contents of mouse gut bacteria. Furthermore, we evaluated the interaction between cerebral metabolites and intestinal microbiota via Pearson correlations. The prediction results suggested that Firmicutes were possibly controlled by neuron integrity, cerebral inflammation, and neurotransmitters, and Bacteroidetes in mouse intestines might be related to cerebral aerobic respiration and the glucose cycle. Such results also implied that Actinobacteria probably affected cerebral energy metabolism. These findings suggested that β-elemene has regulatory effects on the imbalanced microbiota-gut-brain axis caused by obesity and, therefore, would contribute to the future study in on the interplay between cerebral metabolites from different brain regions and the intestinal microbiota of mice. [ABSTRACT FROM AUTHOR]

The article focuses on a research concerning the analysis of two different epitopes including OVA23-3 CD4+T cells and DO11.10 CD4+T cells in the ovalbumin 323-339 (OVA 323-339) peptide of mice or food allergic patients. The research found that OVA23-3 CD4+T identified the Th2-phenotype while DO11.10 CD4+T cells identified the Th1-phenotype. It also discusses the impact of these differences on the immune responses of mice.

To examine novel functions of milk basic protein (MBP) in T-cell-related inflammatory diseases, such as autoimmune diseases and allergies, we evaluated the effects of MBP on the causative responses of ovalbumin (OVA)-specific T cells in a food-allergic enteropathy model, OVA23-3 mice, which express an OVA-specific T-cell receptor gene. The OVA-specific CD4+ T cells of the mesenteric lymph nodes (MLN) from OVA23-3 mice were cultured with CD11c+ dendritic cells of MLN from BALB/cA mice in the absence or presence of MBP following stimulation with OVA; then the levels of CD69 expression and the levels of cytokine production by CD4+ T cells were measured to evaluate activation. The effects of MBP supplementation of OVA 23-3 mice were assessed by feeding a diet containing OVA (OVA diet) with or without MBP for 28 d. Intestinal inflammation, together with activation and cytokine production of CD4+ T cells by MLN, as well as femoral bone mineral density, were measured. In in vitro culture, MBP inhibited excess activation and IL-4 production by CD4+ T cells. The supplementation of MBP to the OVA diet attenuated OVA-specific IgE production in OVA-diet-fed OVA23-3 mice and slightly resolved developing enteropathy caused by excess IL-4 production by CD4+ T cells. Feeding OVA diet to OVA23-3 mice exhibited bone loss accompanied with enteropathy, whereas MBP supplementation prevented bone loss and increased osteoprotegerin, an osteoclastogenesis inhibitory factor, in the mice. The inhibition of T-cell-activation in both MLN and bone marrow by MBP supplementation may help prevent increased IgE levels caused by excessive IL-4 production and bone loss accompanied by enteropathy. Our findings show that MBP may help attenuate both T-cell-related inflammation and bone loss. [ABSTRACT FROM AUTHOR]

Abstract: It has been demonstrated that intestinal commensal bacteria induce immunoglobulin (Ig) A production by promoting the development of gut-associated lymphoid tissues in the small intestine. However, the precise mechanism whereby these bacteria modulate IgA production in the large intestine, which harbors the majority of intestinal commensals, is poorly understood. In addition, it is not known which commensal bacteria induce IgA production in the small intestine and which induce production in the large intestine. To address these issues, we generated gnotobiotic mice mono-associated with different murine commensal bacteria by inoculating germ-free (GF) mice with Lactobacillus johnsonii or Bacteroides acidifaciens. In GF mice, IgA production was barely detectable in the small intestine and was not detected in the large intestine. Interestingly, total IgA secretion in the large intestinal mucosa of B. acidifaciens mono-associated (BA) mice was significantly greater than that of GF and L. johnsonii mono-associated (LJ) mice. However, there was no difference in total IgA production in the small intestine of GF, LJ and BA mice. In addition, in the large intestine of BA mice, the expression of IgA+ cells and germinal center formation were more remarkable than in GF and LJ mice. Furthermore, B. acidifaciens-specific IgA was detected in the large intestine of BA mice. These results suggest that the production of IgA in the large intestine may be modulated by a different mechanism than that in the small intestine, and that B. acidifaciens is one of the predominant bacteria responsible for promoting IgA production in the large intestine. [Copyright &y& Elsevier]

Abstract: Colonization of the gut by commensal bacteria modulates the induction of oral tolerance and allergy. However, how these intestinal bacteria modulate antigen-specific T cell responses induced by oral antigens remains unclear. In order to investigate this, we used germ-free (GF) ovalbumin (OVA)-specific T cell receptor transgenic (OVA23-3) mice. Conventional (CV) or GF mice were administered an OVA-containing diet. Cytokine production by CD4+ cells from spleen (SP), mesenteric lymph nodes (MLN) and Peyer''s patches (PP) was evaluated by ELISA, as was the peripheral antibody titer. T cell phenotype was assessed by flow cytometry. CD4+ cells from the SP and MLN of CV and GF mice fed an OVA diet for 3 weeks produced significantly less IL-2 than the corresponding cells from mice receiving a control diet, suggesting that oral tolerance could be induced at the T cell level in the systemic and intestinal immune systems of both bacterial condition of mice. However, we also observed that the T cell hyporesponsiveness induced by dietary antigen was delayed in the systemic immune tissues and was weaker in the intestinal immune tissues of the GF mice. Intestinal MLN and PP CD4+ T cells from these animals also produced lower levels of IL-10, had less activated/memory type CD45RBlow cells, and expressed lower levels of CTLA-4 but not Foxp3 compared to their CV counterparts. Furthermore, GF mice produced higher serum levels of OVA-specific antibodies than CV animals. CD40L expression by SP CD4+ cells from GF mice fed OVA was higher than that of CV mice. These results suggest that intestinal commensal bacteria promote T cell hyporesponsiveness and down-regulate serum antibody responses induced by dietary antigens through modulation of the intestinal and systemic T cell phenotype. [Copyright &y& Elsevier]

Abstract: Bifidobacterium is a dominant bacterial species among commensals in the human intestine and is thought to have probiotic immunomodulatory effects. In this study, we investigated the effect of the association with Bifidobacterium pseudocatenulatum JCM 7041 (Bp) on dietary ovalbumin (OVA)-specific immune responses using germ-free OVA-specific T cell receptor transgenic mice (OVA23-3 mice). We established germ-free OVA23-3 mice, and then associated with Bp (BIF group) or without (CONT group) and additionally associated with segmented filamentous bacteria (SFB) and clostridia in both groups. BIF and CONT mice were fed an egg-white diet containing OVA for 1 week. Cytokine production in response to OVA by cells of Peyer''s patches (PPs) and lamina propria (LP) from the small and large intestine was measured. Interferon (IFN)-γ and interleukin (IL)-6 production by PP cells from BIF group mice was lower than that of the CONT group. The proportion of PP cells expressing CD4+CD62Llow, an activated/memory T cell phenotype, was higher in BIF group mice than the CONT group. Furthermore, LP cells from the small intestine in Bp-associated mice showed a tendency to produce slightly lower IFN-γ and IL-6, while the cells from large intestine produced markedly higher IFN-γ, IL-5 and IL-6 than those in the CONT group. The pattern of cytokine production by PP in BIF animals was similar to those isolated from conventional mice. These results suggest that intestinal association with Bp might down-regulate excessive immune responses to dietary antigens of the small intestine but enhance those of the large intestine. [Copyright &y& Elsevier]