Introduction
Food allergies are a growing health concern that can lead to serious health complications [21]. Cow’s milk allergy (CMA) is one of the earliest and most prevalent food allergies and bovine β-lactoglobulin (BLG) is the major allergen [5, 17]. Diets based on cow’s milk play a major role in children’s nutrition, and therefore, it is important to effectively prevent and manage this food allergy.
A number of approaches have been proposed for preventing food allergies, including allergen avoidance, allergen reactivity reduction, and immune modulation. At present, the only proven therapy is a strict elimination diet [21]. For common foods, such as cow’s milk or hen’s eggs, absolute avoidance is difficult in everyday life [33]. Many modern processing techniques are used for reducing the antigenicity of food proteins by changing the structure of allergens, such as thermal treatment, glycation, enzymatic hydrolysis, and fermentation. However, allergen reactivity cannot be completely eliminated [29]. More recently, modulation of the host’s immune responses to allergens seems an ideal approach for preventing food allergies, since food allergies are characterized by activation of Thelper type 2 (Th2) T lymphocytes and reduction of T regulatory (Treg) cell activity [26]. The generation of Treg cells can suppress allergen-induced proliferative and cytokine responses in both Th1 and Th2 lymphocytes [2]. Because of this, specific allergen immunotherapy (SIT) is most effectively used for the treatment of food allergies, which results in the generation of Treg cells [3]. Dendritic cells (DCs), the most professional antigen-presenting cells, have a crucial role in the control of the adaptive immune responses by T cell activation. Different subsets of DCs have been described in the intestine of mice based on the expression of CD11c, CD11b, mPDCA, CD80, CD86, MHCII, and CD103 [30, 31]. Regulatory dendritic cells (regDCs) that express high levels of IL-10, TGF-β, and indoleamine-2,3-dioxygenase (IDO) directly mediate the conversion of T cells into Foxp3+ Treg cells and induce immune tolerance [22]. There are two subsets of regDCs; one is immature DCs or semi-mature DCs that express reduced levels of MHCII and co-stimulatory molecules, whereas the other is CD11c+CD103+ DCs that express retinaldehyde dehydrogenase (RALDH) to metabolize vitamin A into retinoic acid [16, 22]. Studies in mouse models indicated that oral sensitization with allergens was accompanied by a shift in intestinal DC subsets towards less CD103+ DCs [31] and this allergic response was alleviated with increased percentages of CD103+ DCs and CD4+CD25+Foxp3+ Treg cells in the mesenteric lymph nodes [26]. However, the mechanism that controls the differentiation and maturation of DCs is not well understood.
Previous studies have indicated that probiotics play crucial roles in preventing food allergies, including hydrolysis of antigenic peptides, modulation of intestinal permeability to reduce systemic penetration of antigens, as well as stimulation of epithelial cell growth and differentiation [4]. Furthermore, it is now widely accepted that probiotics, such as Lactobacillus rhamnosus GG (LGG), which has been shown to be beneficial for treating pediatric allergic disorders, is important for optimal immune homeostasis of the host [18]. It has been indicated that oral probiotics supplementation can shift Th2-dominated trends to Th1-dominated responses in murine allergy models [12, 23]. Bacterial strain-specific induction of Foxp3+ Treg cells has also been demonstrated to be protective in respiratory and food allergy models [11, 25]. Additionally, many probiotics can modulate the expression of cytokines and maturation surface markers in murine DCs, which are required for activation of antigen-specific T cells [37]. Lactobacillus paracasei inhibits Th2-dependent allergic responses to ovalbumin via enhancing PD-L2 expression on dendritic cells [14], but the probiotic-associated influence of regDCs on food allergy in vivo is very poorly understood.
Lactobacillus paracasei L9 (L9) is a commensal bacterial strain originally isolated from the feces of healthy centenarians. L9 has been shown to be effective in the prevention of constipation and ulcerative colitis through regulation of chemokine and cytokine expression [36, 38]; however, to the best of our knowledge, the protective effect of L9 on allergies has not yet been investigated. In the current study, the effects of L9 on the modulation of intestinal and systemic antigen-specific immune responses to BLG were examined.
Materials and Methods
Bacterial Growth
L9 (the name Lactobacillus casei LC-14 had been used before) was grown in MRS medium, supplemented with ʟ-cysteine hydrochloride (0.5 g/l), anaerobically, at 37℃. The bacteria were incubated overnight and the bacterial concentration and viability were then determined by densitometry and by CFU counts after agar plating. Bacteria were collected by centrifugation at 3,000 ×g for 10 min and suspended in aseptic PBS. For in vitro experiments, L9 was adjusted to 1010 CFU/ml in PBS and heat treated at 95℃ for 25 min, and then stored at -80℃ until use.
Animals and Experimental Design
Three-week-old female BALB/c mice were purchased from Charles River Breeding Laboratories (Beijing, China). Mice were housed in stainless steel cages at 22-24℃ on a 12L:12D schedule under specific-pathogen-free conditions. Animals were fed a plantbased chow diet that contained no animal proteins or microbes (Charles River Breeding Laboratories). The Animal Care Committee of China Agricultural University approved these studies.
Mice were divided into three groups (n = 8/group): sham sensitized with PBS as placebo control (CON), BLG-sensitized negative control (BLG), and L9-supplemented BLG (L9). Mice were sensitized intragastrically with BLG (1 mg/g BW; Sigma-Aldrich, St. Louis, MO, USA) plus cholera toxin (CT, 0.3 μg/g BW; Sigma-Aldrich) used as an adjuvant in a total volume of 200 μl of PBS, and administered at weekly intervals for 5 consecutive weeks. L9 was supplemented daily via gavage to L9 mice (2 × 109 CFU in 200 μl of PBS). At 5 weeks after the first oral gavage, all mice were fasted overnight and challenged with a high dose of BLG (50 mg/mouse) intragastrically (Fig. S1). Mice were euthanized 60 min after the last dose of BLG, blood was collected, and the spleen, mesenteric lymph node (MLN), and Peyer’s patches (PP) were removed under sterile conditions and placed in RPMI-1640 medium (Gibco, Grand Island, NY, USA).
Lymphocytes Culture In Vitro
The preparation of lymphocytes isolated from the spleen, MLN and PP were performed and cultured as previously described [11]. MLN and PP were scraped on metal grids and passed through 40 mm nylon cell strainers (BD Falcon, Franklin Lakes, NJ, USA). Splenocytes were collected by flushing PBS into spleens with a 1 ml syringe, and the red blood cells in splenocytes were treated with red blood cell lysis buffer (Beyotime, Nantong, China) and washed with PBS three times. Mononuclear cells, adjusted to 5 × 106 cells/ml, were stimulated with BLG (20 μg/ml) or media alone in 96-well plates in RPMI-1640 culture medium supplemented with 10% heat-inactivated fetal calf serum, 2 mM ʟ-glutamine, 100 U/ml penicillin, and 100 μg/ml streptomycin. The cells were cultured in a humidified incubator at 37℃ with 5% CO2 for 60 h.
Preparation and Activation of Bone Marrow-Derived DCs
Mouse bone marrow-derived DCs (BM-DCs) were prepared as previously described [28], with minor modifications. Briefly, the bone marrow precursors were isolated from the femurs and tibias of mice. Cells were cultured at 5 × 105/ml in culture medium with Recombinant Murine GM-CSF (20 ng/ml; Peprotech, Rocky Hill, NJ, USA) and Recombinant Murine IL-4 (10 ng/ml; Peprotech). Fresh medium was added on days 3 and 6 and BM-DCs were used on day 8. BM-DCs (106 cells/ml) were stimulated with BLG (20 μg/ml), in the culture medium containing heat-inactivated L9 (106 or 107 CFU/ml) for 24 h. Lipopolysaccharide (LPS; Sigma-Aldrich) at 1 μg/ml was used as the positive control.
DC-CD4+T Cell Co-Cultures
After stimulation by L9 (BM-DCs: bacteria = 1:10) and LPS, BMDCs were harvested and pretreated with mitomycin C (25 μg/ml; Sigma-Aldrich) for 1 h to prevent proliferation. BM-DCs (105 cells/ml) were then cultured for 5 days with splenic CD4+ T cells (106 cells/ml), isolated by magnetic bead sorting (CD4+T cell isolation kit; Miltenyi, Bergisch Gladbach, Germany) from BLG mice, in the presence of BLG (20 μg/ml).
Determination of Cytokine Levels and Immunoglobulins
Blood samples were centrifuged (3,500 ×g) for 10 min at 4℃ and serum was collected and frozen at -80℃. Serum histamine, mouse mast cell protease-1 (mMCP-1), and cytokines (IL-4, IL-10, IL-12p70, IFN-γ, and TGF-β) in the serum or culture supernatants were determined using commercial ELISA kits (R&D Systems, Inc., Minneapolis, MN, USA; eBioscience, Vienna, Austria) following the manufacturer’s recommendations. Total serum IgE levels were measured by ELISA, according to the manufacturer's instructions (ICL Lab, Portland, OR, USA).
Levels of BLG-specific IgE, IgG, IgG1, and IgG2a were measured as previously described [28], with minor modifications. Briefly, 96-well plates were coated with 20 μg/ml of BLG in coating buffer (0.5 M Na-bicarbonate/carbonate, pH 9.6). Serum samples were diluted 1:50 for IgE, 1:500 for IgG1 and IgG2a, and 1:1,000 for IgG, prior to being used in the assays. All other procedures, such as washing, blocking, and incubation, were done as previously described [1].
Flow-Cytometry Analysis
Single-cell suspensions of spleens, MLN, PP, or DCs-CD4+T cell co-cultures were preincubated with FcR blocking reagent (Miltenyi) before being stained with a Foxp3 Staining Buffer Set (eBioscience, Auburn, NY, USA). DCs were labeled with monoclonal antibodies for CD11c (FITC), CD103 (PE), MHCII (PerCP-eFluor710), CD80 (APC), or CD86 (PE-Cyanine7) (eBioscience). Cells were analyzed using a FACS Calibur flow cytometer (Becton-Dickinson), and FlowJo 7.6.1 software (TreeStar, Ashland, OR, USA) was used to analyze the data.
Statistical Analysis
Statistical analysis of the differences among groups was evaluated with one-way ANOVA followed by Duncan’s multiplecomparison test using SPSS software (ver. 19.0; SPSS Inc., Chicago, IL, USA). Significant differences were established at the level of p < 0.05. Data are expressed as means ± standard deviations (SD).
Results
L. paracasei L9 Consumption Alleviated Allergic Sensitization of BLG
The most severe reactions were observed in BLG mice and significantly reduced by L9 supplementation (Fig. S2). L9 treatment decreased the BLG-induced histamine and mMCP-1 production (Table 1), and reduced the serum total IgE level by 27.61%, compared with BLG mice (Fig. 1A). In addition, L9 down-regulated the serum level of BLG-specific IgE, IgG, and IgG1, but did not significantly change IgG2a (Fig. 1B). These results confirm L9 treatment prevents allergic sensitization of BLG.
Table 1.Results are expressed as the mean ± SD for each group (n = 8 animals per group). Values with different superscript letters are significantly different (p < 0.05). CON: PBS, control mice; BLG: BLG + CT; L9: BLG + mice supplemented with L9. L9, Lactobacillus paracasei L9; BLG, β-lactoglobulin; CT, cholera toxin.
Fig. 1.Influence of L. paracasei L9 on immunoglobulin levels in serum. Serum from all mice was collected after euthanasia. (A) The level of total IgE in serum. (B) The levels of BLG-specific IgE, IgG, IgG1, and IgG2a in serum. Results are expressed as the mean ± SD for each group (n = 8 animals per group). The values with different superscript letters are significantly different (p < 0.05). CON: PBS, control mice; BLG: BLG + CT; L9: BLG mice supplemented with L9. L9, Lactobacillus paracasei L9; BLG, β-lactoglobulin; CT, cholera toxin.
L. paracasei L9 Supplement Induced CD4+CD25+Foxp3+ Treg Cells to Balance the Disorder of Th1/Th2
Food allergies are characterized by activation of Th2 lymphocytes and reduction of Treg cell activity. The numbers of CD4+CD25+Foxp3+ Treg cells in lymphocytes from the PP, MLN, and spleen of L9 mice were also increased by 27.68%, 51.85%, and 17.50%, respectively, with significantly decreased IL-4 and increased IFN-γ production in lymphocytes (Figs. 2A-2C). As shown in Table 1, the BLG induced production of both Th1 and Th2 related cytokines, IL-12p70 and IL-4 were suppressed, and production of the Th1-related cytokine, IFN-γ, was increased in serum from L9 mice compared with BLG mice. In addition, L9 also significantly increased the levels of the regulatory cytokines TGF-β and IL-10 in serum or culture supernatants (Figs. 2D-2E). All these results suggest L9 is effective in inducing CD4+CD25+Foxp3+ Treg cellmediated tolerance.
Fig. 2.Influence of L. paracasei L9 on the number of CD4+CD25+Foxp3+ Treg cells and cytokine production. Lymphocytes isolated from PP, MLN, and spleen from all groups were determined with flow cytometric analysis. (A) Typical plots depicting percentage of CD25+Foxp3+ within CD4+ cells of lymphocytes isolated from PP, MLN, and spleen from all groups. (B-E) Levels of TGF-β, IL-10, IL-4, and IFN-γ in culture supernatants of lymphocytes from PP, MLN, and spleen were cultured with 20 μg/ml of BLG for 60 h. Results are expressed as the mean ± SD for each group (n = 4-5 animals per group). Values with different superscript letters are significantly different (p < 0.05). CON: PBS, control mice; BLG: BLG + CT; L9: BLG mice supplemented with L9. PP, Peyer’s patches; MLN, mesenteric lymph nodes; L9, Lactobacillus paracasei L9; BLG, β-lactoglobulin; CT, cholera toxin.
L. paracasei L9 Induced regDC and Regulatory Cytokine Production
To evaluate the possible involvement of regDCs in L9-induced hyporesponsiveness, the expression of CD103 and maturation status of DCs were analyzed. The percentages of CD103+DCs in CD11c+DCs were much lower in the PP, MLN, and spleen of BLG-sensitized mice than in CON mice and were significantly increased in L9 mice (Fig. 3B). There were significant decreased percentages of CD80+DCs, CD86+DCs, and MHC-II+DCs in the PP and MLN by L9 consumption, compared with BLG mice (Figs. 3C-3E). Similar results were observed in BM-DCs stimulated by L9 in vitro, with about 1.31-fold increase of CD103+DCs with the enhanced mRNA expression of RALDH2 and IDO (Fig. S3) compared with the negative control, and the expression of CD86 was not significantly changed. However, the levels of MHC-II and CD80 were increased by L9, but lower than the effect of LPS stimulation (Figs. 4A-4E).
Fig. 3.Influence of L. paracasei L9 on CD103 expression and maturation status of DCs in vivo. Lymphocytes isolated from PP, MLN, and spleen from all groups were determined with flow cytometric analysis. (A) Lymphocytes were analyzed by flow cytometry for CD103, CD80, CD86, and MHC-II expression in CD11c+ DCs, and CD11c-FITC was used to gate DCs (grey zone, CON; dotted line, BLG; solid line, L9). (B-E) The percentage of CD103+ DCs, CD80+ DCs, CD86+ DCs, and MHC-II+ DCs in CD11c+ DCs. Results are expressed as the mean ± SD for each group (n = 4-5 animals per group). Values within PP, MLN, or spleen with different superscript letters are significantly different (p < 0.05). CON: PBS, control mice; BLG: BLG + CT; L9: BLG mice supplemented with L9. PP, Peyer’s patches; MLN, mesenteric lymph nodes; L9, Lactobacillus paracasei L9; BLG, β-lactoglobulin; CT, cholera toxin.
Fig. 4.Influence of L. paracasei L9 on CD103 expression, maturation status of DCs, and cytokine production in vitro. BM-DCs from naive BALB/c mice were stimulated with BLG (20 μg/ml), and cultured with medium alone (CON), ultra-pure lipopolysaccharide from E. coli (LPS, 1 μg/ml), or Lactobacillus paracasei L9 (L9, BM-DCs: bacteria = 1:1 or 1:10) for 24 h. (A) BM-DCs were analyzed by flow cytometry for CD103, CD80, CD86, and MHC-II expression in CD11c+ DCs, and CD11c-FITC was used to gate DCs (grey zone, CON; dotted line, LPS; solid line, L9). (B-E) The percentage of CD103+ DCs, CD80+ DCs, CD86+ DCs, and MHC-II+ DCs in CD11c+ DCs at ratio of 1:10 (BM-DCs: bacteria). (F-H) Production of IL-10, TGF-β, and IL-12p70 in culture supernatant was determined. Results of three independently performed experiments are shown as the mean ± SD. Values with different superscript letters are significantly different (p < 0.05). L9 +, BM-DCs: bacteria = 1:1; L9 ++, BMDCs: bacteria = 1:10.
Furthermore, stimulation of BM-DCs by L9 increased regulatory cytokine production dose dependently, such as a 19.57-fold increase in IL-10 and a 1.85-fold increase in TGF-β production at the ratio of 1/10 (BM-DCs: bacteria), similar to LPS stimulation (Figs. 4F-4H). These results suggest L9 induces the expression of CD103 and low maturation status in DCs.
L. paracasei L9-Stimulated DCs Induced Foxp3 Expression
L9-stimulated DCs were incubated with CD4+ T cells from BLG mice in order to investigate the effect of L9-stimulated DCs in inducing Foxp3 expression. As shown in Fig. 5A, Foxp3 expression was 54.27% increased, and there was significantly increased IL-10, TGF-β, and IFN-γ secretion but decreased IL-4 production in L9-stimulated BM-DCs and CD4+ T cell co-cultures, compared with CD4+ T cells incubated with unstimulated DCs (Figs. 5B-5E). These results confirm L9-stimulated DCs induce Foxp3 expression and shift the Th1/Th2 imbalance.
Fig. 5.Influence of L. paracasei L9-stimulated BM-DCs on Foxp3 expression in CD4+T cells and cytokine production in vitro. BM-DCs from naive BALB/c mice were stimulated with BLG (20 μg/ml), and cultured with medium alone (CON), ultra-pure lipopolysaccharide from E. coli (LPS, 1 μg/ml), or Lactobacillus paracasei L9 (L9, BM-DCs: bacteria = 1:10) for 24 h, harvested, pretreated with mitomycin C (25 μg/ml), and then washed and reincubated with CD4+ T cells from BLG mice for 5 days, in the presence of BLG (20 μg/ml). (A) The percentage of CD25+Foxp3+ within CD4+ cells. (B-E) Production of IL-10, TGF-β, and IL-12p70 in culture supernatant. Results of three independently performed experiments are shown as the mean ± SD. Values with different superscript letters are significantly different (p < 0.05).
Discussion
The present study demonstrated the protective effects of L9 on allergic inflammation in BLG-sensitized mice and investigated whether microbial induction of regDCs was associated with this protection. L9 supplementation in mice was found to reduce BLG-induced sensitization, to significantly reduce hypersensitivity scores, and to reduce histamine, mMCP-1, and total or BLG-specific serum IgE concentrations compared with BLG mice. In addition, L9 balanced the BLG-induced disorder of Th1/Th2 (Table 1, Figs. 1 and 2). These findings are in line with previous studies, which showed that probiotics suppressed CMA by manipulating the Th1/Th2 balance [6, 35]. Recent studies have shown that Foxp3+Treg cells, induced by commensal intestinal bacteria, played an important role in regulating allergic responses and in balancing Th1/Th2 polarization [19, 25]. In the current study, L9 significantly increased the number of CD4+CD25+Foxp3+ Treg cells in the MLN and induced high levels of TGF-β and IL-10 in the serum and lymphocyte supernatants from the MLN (Fig. 2), indicating the powerful effect of probiotics on modulating the intestinal immune response. These were similar to results observed in a study of ovalbumin allergy, which showed that LGG only induced the number of CD4+CD25+Foxp3+ Treg cells and TGF-β secretion in the MLN, but not in the spleen [11].
DCs play an important role in routing the immune responses and inducing different T cell subsets, such as the conversion from T cells to Foxp3+ Treg cells [22, 27]. Immature DCs and CD103+DCs are important for establishing tolerance [13, 15]. Previous studies have shown that the oral tolerance to ovalbumin or CMA was improved by high percentages of CD103+ DCs within the gut [26, 34]. It has been reported that various strains and species of lactic acid bacteria regulated DC activation and maturation differentially and that only certain probiotic strains primed DCs for generation of Treg cells [10, 32]. In this study, the number of CD103+DCs was increased by L9 stimulation both in vivo and in vitro (Figs. 3B and 4B), and this stimulation in vitro was associated with a higher level of RALDH2 mRNA expression (Fig. S3). RALDH2 is involved in the retinoic acid-mediated introduction of Foxp+ Treg cells [25]. Previous studies have demonstrated the protective effect of CD103+ DCs on food allergies, through superantigen feeding or continuous oral antigen administration [8, 34]. To the best of our knowledge, there have been no published studies investigating the effects of probiotic-induced CD103+DCs on CMA or food allergies.
In the current study, the percentages of CD80+DCs, CD86+DCs, and MHCII+DCs in lymphocytes of the PP and MLN were reduced in L9 mice, compared with BLG mice (Figs. 3C and 3E). In constrast, MHC-II and CD80 expression levels in BM-DCs were increased by L9 in vitro (Figs. 4D and 4E). However, although the L9-stimulated BM-DCs seemed to have matured, the production of TGF-β and IL-10 of BM-DCs was increased, with increased Foxp3+ expression in CD4+ T cells from BLG mice, and induced a shift in the Th1/Th2 paradigm in DC-CD4+T cell co-cultures (Fig. 5). Recent studies have shown the suppressing effect of CD4+CD25+Foxp3+ Treg cells on Th1 and (or) Th2 cells [9, 25]. Similar results were observed in a previous study, in which CD80 and CD86 were upregulated when DCs were exposed to probiotics in vitro; however, these DCs in that study also induced the number of CD4+CD25+Foxp3+ Treg cells [20]. Other studies have shown that lactobacilli from the gut flora induced semimature DCs, which expressed high levels of MHCII and IL-10, but low levels of IL-12p70, and were actively tolerogenic via the induction of Treg cells [7, 24]. Taken together, our data suggest that L9 includes CD4+CD25+Foxp3+ Treg cells, possibly by CD103+DCs or semi-mature DCs dependent mechanisms. To the best of our knowledge, there are few published studies investigating the tolerogenic capacity of CD103+DCs or semi-mature DCs stimulated by probiotics in food allergy models.
In summary, data from this study clearly show that oral supplementation of probiotics can reduce the development of allergic sensitization to BLG, through maintaining the intestinal and systemic immune responses. This suggests that the manipulation of CD11c+CD103+ DCs and semimature DCs, by potential probiotics, is important for preventing antigen-specific immune reactions.
References
- Adel-Patient K, Créminon C, Bernard H, Clément G, Négroni L, Frobert Y, et al. 2000. Evaluation of a high IgEresponder mouse model of allergy to bovine β-lactoglobulin (BLG): development of sandwich immunoassays for total and allergen-specific IgE, IgG1 and IgG2a in BLG-sensitized mice. J. Immunol. Methods 235: 21-32. https://doi.org/10.1016/S0022-1759(99)00210-0
- Akdis M, Akdis CA. 2009. Therapeutic manipulation of immune tolerance in allergic disease. Nat. Rev. Drug Discov. 8: 645-660. https://doi.org/10.1038/nrd2653
- Akdis M, Blaser K, Akdis CA. 2005. T regulatory cells in allergy: novel concepts in the pathogenesis, prevention, and treatment of allergic diseases. J. Allergy Clin. Immun. 116: 961-968. https://doi.org/10.1016/j.jaci.2005.09.004
- Berni CR, Di CM, Pezzella V, Cosenza L, Granata V, Terrin G, et al. 2012. The potential therapeutic efficacy of Lactobacillus GG in children with food allergies. Pharmaceuticals 5: 655-664. https://doi.org/10.3390/ph5060655
- Braun FC, Von Mutius E. 2011. Can farm milk consumption prevent allergic diseases? Clin. Exp. Allergy 41: 29-35. https://doi.org/10.1111/j.1365-2222.2010.03665.x
- Canani RB, Di Costanzo M. 2013. Gut microbiota as potential therapeutic target for the treatment of cow’s milk allergy. Nutrients 5: 651-662. https://doi.org/10.3390/nu5030651
- Christensen HR, Frøkiær H, Pestka JJ. 2002. Lactobacilli differentially modulate expression of cytokines and maturation surface markers in murine dendritic cells. J. Immunol. 168: 171-178. https://doi.org/10.4049/jimmunol.168.1.171
- Coombes JL, Siddiqui KR, Arancibia-Cárcamo CV, Hall J, Sun C, Belkaid Y, et al. 2007. A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-β– and retinoic acid–dependent mechanism. J. Exp. Med. 204: 1757-1764. https://doi.org/10.1084/jem.20070590
- Dehzad N, Bopp T, Reuter S, Klein M, Martin H, Ulges A, et al. 2011. Regulatory T cells more effectively suppress Th1-induced airway inflammation compared with Th2. J. Immunol. 186: 2238-2244. https://doi.org/10.4049/jimmunol.1002027
- Elawadli I, Brisbin JT, Mallard BA, Griffiths MW, Corredig M, Sharif S. 2014. Differential effects of lactobacilli on activation and maturation of mouse dendritic cells. Benef. Microbes 5: 323-334. https://doi.org/10.3920/BM2013.0066
- Finamore A, Roselli M, Britti MS, Merendino N, Mengheri E. 2012. Lactobacillus rhamnosus GG and Bifidobacterium animalis MB5 induce intestinal but not systemic antigenspecific hyporesponsiveness in ovalbumin-immunized rats. J. Nutr. 142: 375-381. https://doi.org/10.3945/jn.111.148924
- Frei R, Lauener RP, Crameri R, O’Mahony L. 2012. Microbiota and dietary interactions – an update to the hygiene hypothesis? Allergy 67: 451-461. https://doi.org/10.1111/j.1398-9995.2011.02783.x
- Fujita S, Sato Y, Sato K, Eizumi K, Fukaya T, Kubo M, et al. 2007. Regulatory dendritic cells protect against cutaneous chronic graft-versus-host disease mediated through CD4+ CD25+ Foxp3+ regulatory T cells. Blood 110: 3793-3803. https://doi.org/10.1182/blood-2007-04-086470
- Inamine A, Sakurai D, Horiguchi S, Yonekura S, Hanazawa T, Hosokawa H, et al. 2012. Sublingual administration of Lactobacillus paracasei KW3110 inhibits Th2-dependent allergic responses via upregulation of PD-L2 on dendritic cells. Clin. Immunol. 143: 170-179. https://doi.org/10.1016/j.clim.2012.01.008
- Jaensson E, Uronen-Hansson H, Pabst O, Eksteen B, Tian J, Coombes JL, et al. 2008. Small intestinal CD103+ dendritic cells display unique functional properties that are conserved between mice and humans. J. Exp. Med. 205: 2139-2149. https://doi.org/10.1084/jem.20080414
- Jeong Y, Kim SH, Ju JW, Cho SH, Lee WJ, Park JW, et al. 2011. Clonorchis sinensis-derived total protein attenuates airway inflammation in murine asthma model by inducing regulatory T cells and modulating dendritic cell functions. Biochem. Biophys. Res. Commun. 407: 793-800. https://doi.org/10.1016/j.bbrc.2011.03.102
- Jo J, Garssen J, Knippels L, Sandalova E. 2014. Role of cellular immunity in cow’s milk allergy: pathogenesis, tolerance induction, and beyond. Mediat. Inflamm. 2014: 1-9. https://doi.org/10.1155/2014/249784
- Kandasamy M, Selvakumari Jayasurya A, Moochhala S, Huat Bay B, Kun Lee Y, Mahendran R. 2011. Lactobacillus rhamnosus GG secreting an antigen and interleukin-2 translocates across the gastrointestinal tract and induces an antigen specific immune response. Microbiol. Immunol. 55: 704-714. https://doi.org/10.1111/j.1348-0421.2011.00370.x
- Kanjarawi R, Dy M, Bardel E, Sparwasser T, Dubois B, Mecheri S, et al. 2013. Regulatory CD4+ Foxp3+ T cells control the severity of anaphylaxis. PLoS One 8: e69183. https://doi.org/10.1371/journal.pone.0069183
- Konieczna P, Groeger D, Ziegler M, Frei R, Ferstl R, Shanahan F, et al. 2012. Bifidobacterium infantis 35624 administration induces Foxp3 T regulatory cells in human peripheral blood: potential role for myeloid and plasmacytoid dendritic cells. Gut 61: 354-366. https://doi.org/10.1136/gutjnl-2011-300936
- Kumar S, Verma AK, Das M, Dwivedi PD. 2012. Molecular mechanisms of IgE mediated food allergy. Int. Immunopharmacol. 13: 432-439. https://doi.org/10.1016/j.intimp.2012.05.018
- Kwon H, Lee C, So J, Chae C, Hwang J, Sahoo A, et al. 2010. Generation of regulatory dendritic cells and CD4+ Foxp3+ T cells by probiotics administration suppresses immune disorders. Proc. Natl. Acad. Sci. USA 107: 2159-2164. https://doi.org/10.1073/pnas.0904055107
- Lee J, Bang J, Woo H. 2013. Effect of orally administered Lactobacillus brevis HY7401 in a food allergy mouse model. J. Microbiol. Biotechnol. 23: 1636-1640. https://doi.org/10.4014/jmb.1306.06047
- Lutz MB, Schuler G. 2002. Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity? Trends Immunol. 23: 445-449. https://doi.org/10.1016/S1471-4906(02)02281-0
- Lyons A, O’Mahony D, O’Brien F, MacSharry J, Sheil B, Ceddia M, et al. 2010. Bacterial strain-specific induction of Foxp3+ T regulatory cells is protective in murine allergy models. Clin. Exp. Allergy 40: 811-819.
- Meulenbroek LA, Esch BC, Hofman GA, Hartog Jager CF, Nauta AJ, Willemsen LE, et al. 2013. Oral treatment with β-lactoglobulin peptides prevents clinical symptoms in a mouse model for cow’s milk allergy. Pediat. Allerg. Immunol. 24: 656-664. https://doi.org/10.1111/pai.12120
- Ross AC. 2012. Vitamin A and retinoic acid in T cell–related immunity. Am. J. Clin. Nutr. 96: 1166S-1172S. https://doi.org/10.3945/ajcn.112.034637
- Schwarzer M, Srutkova D, Schabussova I, Hudcovic T, Akgün J, Wiedermann U, et al. 2013. Neonatal colonization of germ-free mice with Bifidobacterium longum prevents allergic sensitization to major birch pollen allergen Bet v 1. Vaccine 46: 5405-5412. https://doi.org/10.1016/j.vaccine.2013.09.014
- Shriver SK, Yang WW. 2011. Thermal and nonthermal methods for food allergen control. Food Eng. Rev. 3: 26-43. https://doi.org/10.1007/s12393-011-9033-9
- Shurin MR, Naiditch H, Zhong H, Shurin GV. 2011. Regulatory dendritic cells. Cancer Biol. Ther. 11: 988-992. https://doi.org/10.4161/cbt.11.11.15543
- Smit JJ, Bol Schoenmakers M, Hassing I, Fiechter D, Boon L, Bleumink R, et al. 2011. The role of intestinal dendritic cells subsets in the establishment of food allergy. Clin. Exp. Allergy 41: 890-898. https://doi.org/10.1111/j.1365-2222.2011.03738.x
- So J, Lee C, Kwon H, Yi H, Chae C, Park J, et al. 2008. Lactobacillus casei potentiates induction of oral tolerance in experimental arthritis. Mol. Immunol. 46: 172-180. https://doi.org/10.1016/j.molimm.2008.07.038
- Staden U, Rolinck Werninghaus C, Brewe F, Wahn U, Niggemann B, Beyer K. 2007. Specific oral tolerance induction in food allergy in children: efficacy and clinical patterns of reaction. Allergy 62: 1261-1269. https://doi.org/10.1111/j.1398-9995.2007.01501.x
- Stern A, Wold AE, Östman S. 2013. Neonatal mucosal immune stimulation by microbial superantigen improves the tolerogenic capacity of CD103+ dendritic cells. PLoS One 8: e75594. https://doi.org/10.1371/journal.pone.0075594
- Thang CL, Baurhoo B, Boye JI, Simpson BK, Zhao X. 2011. Effects of Lactobacillus rhamnosus GG supplementation on cow’s milk allergy in a mouse model. Allergy Asthma Clin. Immunol. 7: 20-28. https://doi.org/10.1186/1710-1492-7-20
- Wang XX, Ren QR, Fu TJ, Zhang WB, Ren FZ, Gan BG. 2013. Preventive effects of Lactobacillus casei-14 on ulcerative colitis in mice. J. Gansu Agric. Univ. 48: 1-5.
- You J, Dong H, Mann ER, Knight SC, Yaqoob P. 2014. Probiotic modulation of dendritic cell function is influenced by ageing. Immunobiology 219: 138-148. https://doi.org/10.1016/j.imbio.2013.08.012
- Zhou XD, Liu AP, Zhang M, Guo HY, Ren FZ. 2012. Laxative effect of lactobacillus paracasei subsp. paracasei LC-01 in constipated mice. J. Dairy Sci. Technol. 35: 7-11.
Cited by
- Allergy and the microbiome of the intestine - part II vol.58, pp.4, 2015, https://doi.org/10.1016/s0415-6412(15)30066-7
- Probiotics and allergic diseases vol.6, pp.1, 2016, https://doi.org/10.5411/wji.v6.i1.75
- Oral administration of Lactobacillus paracasei L9 attenuates PM 2.5 -induced enhancement of airway hyperresponsiveness and allergic airway response in murine model of asthma vol.12, pp.2, 2015, https://doi.org/10.1371/journal.pone.0171721
- The regulation of immune cells by Lactobacilli: a potential therapeutic target for anti-atherosclerosis therapy vol.8, pp.35, 2015, https://doi.org/10.18632/oncotarget.18346
- Oral administration of Clostridium butyricum CGMCC0313-1 inhibits β-lactoglobulin-induced intestinal anaphylaxis in a mouse model of food allergy vol.9, pp.None, 2015, https://doi.org/10.1186/s13099-017-0160-6
- Effect of Lactobacillus acidophilus KLDS 1.0738 on miRNA expression in in vitro and in vivo models of β-lactoglobulin allergy vol.82, pp.11, 2018, https://doi.org/10.1080/09168451.2018.1495551
- Global Transcriptomic Analysis and Function Identification of Malolactic Enzyme Pathway of Lactobacillus paracasei L9 in Response to Bile Stress vol.9, pp.None, 2018, https://doi.org/10.3389/fmicb.2018.01978
- Growth Performance and Post-Weaning Diarrhea in Piglets Fed a Diet Supplemented with Probiotic Complexes vol.28, pp.11, 2018, https://doi.org/10.4014/jmb.1807.07026
- Changes in intestinal gene expression and microbiota composition during late pregnancy are mouse strain dependent vol.8, pp.None, 2015, https://doi.org/10.1038/s41598-018-28292-2
- Cutting Edge: Probiotics and Fecal Microbiota Transplantation in Immunomodulation vol.2019, pp.None, 2019, https://doi.org/10.1155/2019/1603758
- Immune-Inflammation in Atherosclerosis: A New Twist in an Old Tale vol.20, pp.4, 2015, https://doi.org/10.2174/1871530319666191016095725
- Regulatory Dendritic Cells, T Cell Tolerance, and Dendritic Cell Therapy for Immunologic Disease vol.12, pp.None, 2021, https://doi.org/10.3389/fimmu.2021.633436
- A New Formulation of Probiotics Attenuates Calcipotriol-Induced Dermatitis by Inducing Regulatory Dendritic Cells vol.12, pp.None, 2015, https://doi.org/10.3389/fimmu.2021.775018
- Immunomodulation of dendritic cells by Lactobacillus reuteri surface components and metabolites vol.9, pp.2, 2015, https://doi.org/10.14814/phy2.14719
- Application of the Combination of Soybean Lecithin and Whey Protein Concentrate 80 to Improve the Bile Salt and Acid Tolerance of Probiotics vol.31, pp.6, 2021, https://doi.org/10.4014/jmb.2103.03017
- The gut microbiome-immune axis as a target for nutrition-mediated modulation of food allergy vol.114, pp.None, 2015, https://doi.org/10.1016/j.tifs.2021.05.021