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Background: Recent data suggested that non-gastrointestinal exposure can lead to sensitisation to food allergens. We thus assessed the immune impact of respiratory or cutaneous exposure to peanut proteins on non-altered epithelium and investigated the effect of such pre-exposure on subsequent oral administration of peanut. Methods: BALB/cJmice were exposed to purified Ara h 1 or to a non-defatted roasted peanut extract (PE) by simple deposit of allergens solutions on non-altered skin or in the nostrils. Exposures were performed 6 times at weekly intervals. Pre-exposed mice then received intra-gastric administrations of PE alone or in the presence of the Th2 mucosal adjuvant cholera toxin (CT). The specific humoral and cellular immune response was assessed throughout the protocol. Results: Bothcutaneous and respiratory exposures led to the production of specific IgG1. Local and systemic IL-5 and IL-13 production were also evidenced, demonstrating activation of specific Th2 cells. This effect was dose-dependent and most efficient via the respiratory route. Moreover, these pre-exposures led to the production of specific IgE antibodies after gavage with PE, whatever the presence of CT. Conclusions: Cutaneous or respiratory exposures to peanut induce Th2 priming in mice. Moreover, pre-exposures promote further sensitisation via the oral route without the use of CT; this proposes a new adjuvant-free experimental model of sensitisation to food that may reflect a realistic exposure pattern in infants. These results also suggest that non-gastrointestinal peanut exposure should be minimised in high-risk infants, even those with non-altered skin, to potentially reduce allergic sensitisation to this major food allergen. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Regulatory T cells contribute to peripheral immune tolerance, yet their ability to control immediate-type hypersensitivity (ITH) reactions involved in IgE-mediated food allergy is still poorly documented. Objectives: We investigated in mice whether CD4+CD25+ regulatory T cells could control ITH to β-lactoglobulin (BLG), a major allergen in cow's milk. Methods: C3H/HeOuJ mice were sensitized by repeated oral gavage with BLG plus cholera toxin as adjuvant and orally challenged with BLG alone to elicit allergic symptoms. Mice were treated with the anti-CD25 mAb (PC61) before sensitization. Oral sensitization (afferent phase of ITH) was assessed by production of BLG-specific serum antibodies and Th1/Th2-type cytokines by specific CD4+ T cells in mesenteric lymph nodes. ITH was elicited by oral BLG challenge (efferent phase of ITH) and we monitored symptom scores, numbers and function of intestinal mast cells and serum level of the mucosal mast cell protease mMCP-1. Results: Upon oral BLG challenge, orally sensitized mice developed only mild clinical signs. Anti-CD25 mAb-treated mice exhibited enhancement of both BLG-specific CD4+ T cell priming with IL-4, IL-5, IL-13 and IFN-γ production and total IgE, and BLG-specific IgE, IgG1 and IgG2a in serum. Anti-CD25 mAb treatment caused more severe symptoms upon BLG challenge, which correlated with enhanced serum levels of the mucosal mast cell protease mMCP-1. Conclusions: These data document that constitutive CD4+CD25+ regulatory T cells alleviate clinical signs of ITH to dietary BLG by modulating the priming of BLG-specific T and B cell responses during oral sensitization and enhancing mast cell degranulation. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: In the last years, the use of probiotics such as lactic acid bacteria (LAB) has been proposed as an attractive alternative for the management of allergic diseases. A partial prevention from sensitization to bovine β-lactoglobulin (BLG), one of the major cows’ milk allergens, could be achieved in mice after intranasal administration with a recombinant LAB strain, Lactococcus lactis, producing BLG (LL-BLG). This study aimed to evaluate the effects of the LL-BLG strain in a therapeutic protocol. Methods: Three groups of mice were first orally sensitized to cows’ milk and then intranasally administered with either the LL-BLG strain, BLG protein alone or saline solution. Serum samples were collected to analyze BLG-specific IgE, IgG1 and IgG2a, and mice were further intranasally challenged with BLG to elicit a specific allergic reaction. Results: Treatment with LL-BLG, but not with BLG alone, contributed to diminish IgG1 production in serum and bronchoalveolar lavage fluids. This was associated with decreased IL-4 production and enhanced IFN-γ production by BLG-reactivated splenocytes, suggesting a switch from Th2- to Th1-immune response. Furthermore, we observed that administration of LL-BLG or LL locally reduced the allergic reaction induced after intranasal challenge, as evidenced by decreased release of IL-4 in bronchoalveolar lavage fluids. Conclusion: These preliminary results demonstrate the efficiency of the intranasal administration of LL-BLG for specific therapy against cows’ milk-related allergy. Copyright © 2009 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The noninvasive and food-grade Gram-positive bacterium Lactococcus lactis is well adapted to deliver medical proteins to the mucosal immune system. In the last decade, the potential of live recombinant lactococci to deliver such proteins to the mucosal immune system has been investigated. This approach offers several advantages over the traditional systemic injection, such as easy administration and the ability to elicit both systemic and mucosal immune responses. This paper reviews the current research and advances made with recombinant L. lactis as live vector for the in situ delivery of biologically active interleukin-12, a potent pleiotropic cytokine with adjuvant properties when co-delivered with vaccinal antigens, at mucosal surfaces. Three well-illustrated examples demonstrate the high potential of interleukin-12-secreting lactococci strains for future prophylactic and therapeutic uses. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: CpG oligonucleotides might offer an alternative to conventional immunotherapy in preventing and potentially reversing Th2-biased immune deregulation which leads to allergy. However, non-invasive ways of administration, especially in peanut-allergic patients, should be explored. Methods: One hundred micrograms of whole peanut protein extract (PE) alone, or mixed with cholera toxin (CT, 50 μg) plus CpG (100 μg) as adjuvant, was applied on intact skin of mice (40 min, twice). Initiation of an immune response was monitored by detection of specific antibodies in sera. The effect of this pretreatment on a further oral sensitization by PE was then evaluated by assaying antibodies and cytokines specific for PE and purified allergens. Cytokine production in liver 40 min after skin application was also assayed. Results: Two brief skin applications of PE alone highly potentiated further oral sensitization, as demonstrated by very intense specific IgE, IL-4 and IL-5 productions. Conversely, skin pretreatment with PE and CT + CpG efficiently prevented further sensitization via gastro-intestinal exposure. In both cases, the specificity of the antibodies and cytokines was the same as in control mice. CT + CpG treatment allowed the rapid production of IL-12 and TGFβ in liver and of specific IgG2a in sera, suggesting the activation of Th1 and/or regulatory T cells. Conclusions: Oral sensitization to peanut is highly enhanced by a previous short exposure of allergens to intact skin. Conversely, the use of CT + CpG adjuvant for skin application efficiently prevents further oral sensitization. The potential of such treatment in specific immunotherapy needs to be evaluated. Copyright © 2007 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Immunoglobulin E (IgE) epitopes of β-lactoglubulin (βLG) have been identified by ELISA inhibition methods using sera from allergic patients. However, the functional capacity of these epitopes to stimulate mast cells is unknown. It is the goal of the present study to identify bivalent IgE epitopes of βLG able to trigger target mast cells. Methods:Peptides were obtained either by purification from tryptic hydrolysates of βLG or by synthesis. They were examined for their triggering activity in vitro on peritoneal 3H-serotonin-labeled rat mast cells passively sensitized with IgE anti-βLG antibodies. In vivo, rats immunized with βLG were administered peptides by gavage for intestinal rat mast cell protease II release. Results: Compared with intact βLG, purified or synthetic tryptic-like βLG peptides have a sharply decreased allergenicity. Peptide 149–162 retains the highest bivalent IgE epitope-mediated triggering capacity. Conclusion: A functional bivalent IgE epitope was identified at the C terminal end of βLG. Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Various studies have shown that DNA immunisation with gene allergen induces a non-allergic response. Methods: We applied this new type of vaccination to bovine β-lactoglobulin (BLG), a major cow’s milk allergen, using a plasmid that allows the production of a partially secreted protein. Specific antibodies and cytokines were quantified in different immunisation protocols. Results: The primary response in mice immunised with BLG-encoding plasmid (pBLG) is of the Th1 type. Restricted recognition of a native form of BLG in pBLG mice contrasted with a broader range of recognition in BLG-in-alum-immunised mice, notwithstanding the fact that alum favours the presentation of a native form of the antigen. We also demonstrated an inhibitory effect of pDNA immunisation on the Th2 response induced by a subsequent immunisation using BLG adsorbed on alum. However, this preventive effect is highly dependent on the time of pre-administration of the pBLG, with an optimal effect when pDNA immunisation occurred at least 21 days before protein administration. This preventive effect resulted concomitantly in the inhibition of BLG-specific IgE, in the induction of specific IgG2a, and in the decrease of the specific IgG1/IgG2 ratio. It is accompanied by an increase in IFNγ and IL-10 secretion. Moreover, the preventive effect was shown to be persistent even after a booster immunisation with alum-adsorbed BLG. The Th1 orientation of the response is very likely due to the presentation of the protein in the Th1 environment due to plasmid immunostimulatory sequences, as intramuscular injection of BLG itself leads to a weak Th2 response and had no preventive effect on a subsequent sensitisation. Conclusion: This study further demonstrates the potential use of DNA immunisation for prevention of IgE response, but the window of action seems to be very restricted if we are to inhibit an established Th2 response efficiently.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]