Dry roasting enhances peanut-induced allergic sensitization across mucosal and cutaneous routes in mice.
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ABSTRACT:
SUBMITTER: Moghaddam AE
PROVIDER: S-EPMC4861634 | biostudies-literature | 2014 Dec
REPOSITORIES: biostudies-literature
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Dry roasting enhances peanut-induced allergic sensitization across mucosal and cutaneous routes in mice.
Moghaddam Amin E AE Hillson William R WR Noti Mario M Gartlan Kate H KH Johnson Steven S Thomas Benjamin B Artis David D Sattentau Quentin J QJ
The Journal of allergy and clinical immunology 20140922 6
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Project description:BackgroundLegume consumption has increased during the two past decades. In France, legumes are responsible for 14.6% of food-related anaphylaxis in children, with peanut as the main allergen (77.5%). Few studies have demonstrated cross-reactivities between peanut and other legumes. The aim of this study was to determine prevalence and relevance of sensitization to legumes in peanut-allergic children.MethodsAll children, aged of 1-17 years, admitted to the Pediatric Allergy Department of the University Hospital of Nancy between January 1, 2017 and February 29, 2020 with a confirmed peanut allergy (PA) and a documented consumption or sensitization to at least one other legume were included. Data were retrospectively collected regarding history of consumption, skin prick tests, specific immunoglobulin E (IgE), prior allergic reactions, and oral food challenges for each legume.ResultsAmong the 195 included children with PA, 122 were sensitized to at least one other legume (63.9%). Main sensitizations were for fenugreek (N = 61, 66.3%), lentil (N = 38, 42.2%), soy (N = 61, 39.9%), and lupine (N = 63, 34.2%). Among the 122 sensitized children, allergy to at least one legume was confirmed for 34 children (27.9%), including six children who had multiple legume allergies (4.9%). Lentil, lupine, and pea were the main responsible allergens. Half of allergic reactions to legumes other than peanut were severe.ConclusionThe high prevalence of legume sensitization and the frequent severe reactions reported in children with PA highlight that tolerated legume consumption should be explored for each legume in the case of PA, and sensitization should be investigated if not.
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Project description:BackgroundOral exposure to food allergens may be limited in infancy, and the initial site of antigen exposure likely plays an important role in food allergy induction.ObjectiveTo examine the impact of different routes of exposure by using milk allergens, with and without adjuvant, on sensitization.MethodsC3H/HeJ mice were repeatedly exposed to the milk allergen ?-lactalbumin (ALA), with or without cholera toxin (CT). Sensitization routes used were intragastric, cutaneous, intranasal, and sublingual. Anaphylaxis severity was assessed by symptoms and body temperature in response to oral challenge. Antigen-specific serum antibodies were measured by ELISA. The mechanism of adjuvant activity of cutaneous CT was also determined.ResultsSensitization to ALA as measured by allergen-specific IgE occurred by all routes of sensitization and was maximal in response to cutaneous exposure. Sensitization was dependent on CT and did not occur to antigen alone by any route. Mucosal, but not cutaneous, exposure resulted in a robust allergen-specific IgA response. Anaphylaxis occurred in all sensitized groups when orally challenged with ALA. Topical CT induced migration of langerin(neg) dermal dendritic cells to the lymph node, resulting in enhanced proliferation and T(H)2 cytokine production from responder T cells.ConclusionsSensitization can occur via all physiologic routes when adjuvant is present. The skin is a potent and likely important physiologic route of sensitization whereby adjuvant induces an efflux of antigen-bearing dermal dendritic cells to the lymph node that generate a proallergic T(H)2 response.
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Project description:ScopeProcessing of food has been shown to impact IgE binding and functionality of food allergens. In the present study, we investigated the impact of heat processing on the sensitization capacity of Ara h 6, a major peanut allergen and one of the most potent elicitors of the allergic reaction.Methods and resultsPeanut extracts obtained from raw or heat-processed peanut and some fractions thereof were biochemically and immunochemically characterized. These extracts/fractions, purified Ara h 6, or recombinant Ara h 6 including Ara h 6 mutants lacking disulfide bridges were used in in vitro digestion tests and mouse models of experimental sensitization. Peanut roasting led to the formation of complexes of high molecular weight, notably between Ara h 6 and Ara h 1, which supported the induction of IgE specific to native Ara h 6. On the contrary, a fraction containing free monomeric 2S albumins or purified native Ara h 6 displayed no intrinsic allergenicity. In addition to complex formation, heat denaturation and/or partial destabilization enhanced Ara h 6 immunogenicity and increased its sensitivity to digestion.ConclusionThese results suggest that sensitization potency and IgE binding capacity can be supported by different structures, modified and/or produced during food processing in interaction with other food constituents.
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Project description:BackgroundAnti-peanut immunoglobulin E (anti-Pn IgE) can persist throughout life, suggesting that this condition could be maintained by long-lived antibody-secreting cells (ASCs). To determine the role of long-lived ASCs, peanut-allergic mice underwent prolonged treatment with the proteasome inhibitor, bortezomib (Bz).MethodsIntravenous Bz was given twice weekly for 21 weeks to peanut-allergic mice. During treatment, serum anti-Pn IgE was measured, and the mice were rechallenged at the end of treatment. Cell populations were measured, and Pn-specific IgG, total IgG, and total IgE ASCs were enumerated in the bone marrow (BM) and spleen (SPL).ResultsProlonged treatment with Bz significantly reduced serum anti-Pn IgE and IgG1 but did not affect symptoms following challenge with Pn, even in mice with undetectable serum anti-Pn IgE. Numbers of CD138+ cells were significantly reduced in the BM but were unaffected in the SPL. Unexpectedly, Bz did not affect numbers of Pn-specific IgG, total IgG, or total IgE ASCs in either the BM or SPL.ConclusionsCells that maintain long-lived serum anti-Pn IgE are sensitive to Bz. However, prolonged depletion of serum Pn-specific IgE does not result in a decrease of symptoms following challenge with Pn.
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Project description:Whether epigenetic factor UTX, a histone H3 lysine 27 (H3K27) demethylase, is critical for type 2 immunity, including allergic sensitization and antigen-driven anaphylaxis, is unclear. We used UTXfl/fl x Lck-Cre mice with UTX-deficient T cells (UTX-TCD) to determine whether T cell-specific UTX expression regulates antigen-specific IgE production after airway sensitization to peanut and anaphylaxis following intraperitoneal (i.p.) peanut challenge. UTX-TCD mice sensitized via the airway with peanut and lipopolysaccharide (LPS), a bacterial component and environmental adjuvant found in house dust, made 2-fold less peanut-IgE and 3.5-fold less peanut-IgG1 than comparably sensitized UTXfl/fl mice, despite higher total IgE and total IgG1 serum antibody levels pre-sensitization. Peanut-induced anaphylaxis was blunted in UTX-TCD mice, with maximum drop in core body temperature after i.p. peanut challenge two-fold lower than in UTXfl/fl mice. Compared to UTXfl/fl controls, UTX-TCD mice had reduced frequencies of CD4+ T-follicular helper (Tfh) cells and germinal center B cells, but higher frequencies of IL-4+ T-helper (Th)2, Tfh2, and IL-13+ Tfh13 cells in airway-draining mediastinal lymph nodes. UTX-TCD mice also skewed toward type 2 antibody and T-helper immune responses independent of allergic sensitization, with fewer IL-10-producing splenic Treg and T-follicular regulatory (Tfr) cells. Our results suggest that UTX expression in T cells impact the production of antigen-specific antibody responses required for allergic sensitization and antigen-specific allergic reactions, suggesting a role for H3K27 histone demethylase UTX in regulating type 2 immunity.
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Project description:Immunoglobulin A (IgA) is the dominant antibody isotype in the gut and has been shown to regulate microbiota. Mucosal IgA is also widely believed to prevent food allergens from penetrating the gut lining. Even though recent work has elucidated how bacteria-reactive IgA is induced, little is known about how IgA to food antigens is regulated. Although IgA is presumed to be induced in a healthy gut at steady state via dietary exposure, our data do not support this premise. We found that daily food exposure only induced low-level, cross-reactive IgA in a minority of mice. In contrast, induction of significant levels of peanut-specific IgA strictly required a mucosal adjuvant. Although induction of peanut-specific IgA required T cells and CD40L, it was T follicular helper (TFH) cell, germinal center, and T follicular regulatory (TFR) cell-independent. In contrast, IgG1 and IgE production to peanut required TFH cells. These data suggest an alternative paradigm in which the cellular mechanism of IgA production to food antigens is distinct from IgE and IgG1. We developed an equivalent assay to study this process in stool samples from healthy, nonallergic humans, which revealed substantial levels of peanut-specific IgA that were stable over time. Similar to mice, patients with loss of CD40L function had impaired titers of gut peanut-specific IgA. This work challenges two widely believed but untested paradigms about antibody production to dietary antigens: (i) the steady state/tolerogenic response to food antigens includes IgA production and (ii) TFH cells drive food-specific gut IgA.
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Project description:Symptom occurrence at the first ingestion suggests that food allergy may result from earlier sensitization via non-oral routes. We aimed to characterize the cellular populations recruited at various mucosal and immune sites after experimental sensitization though different routes. BALB/cJ mice were exposed to a major allergenic food (peanut) mixed with cholera toxin via the intra-gastric (i.g.), respiratory, cutaneous, or intra-peritoneal (i.p.) route. We assessed sensitization and elicitation of the allergic reaction and frequencies of T cells, innate lymphoid cells (ILC), and inflammatory and dendritic cells (DC) in broncho-alveolar lavages (BAL), lungs, skin, intestine, and various lymph nodes. All cellular data were analyzed through non-supervised and supervised uni/multivariate analysis. All exposure routes, except cutaneous, induced sensitization, but intestinal allergy was induced only in i.g.- and i.p.-exposed mice. Multivariate analysis of all cellular constituents did not discriminate i.g. from control mice. Conversely, respiratory-sensitized mice constituted a distinct cluster, characterized by high local inflammation and immune cells recruitment. Those mice also evidenced changes in ILC frequencies at distant site (intestine). Despite absence of sensitization, cutaneous-exposed mice evidenced comparable changes, albeit less intense. Our study highlights that the initial route of sensitization to a food allergen influences the nature of the immune responses at various mucosal sites. Interconnections of mucosal immune systems may participate in the complexity of clinical manifestations as well as in the atopic march.
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Project description:Increasing numbers of clinical trials and animal experiments have shown that probiotic bacteria are promising tools for allergy prevention. Here, we analyzed the immunomodulatory properties of three selected lactobacillus strains and the impact of their mixture on allergic sensitization to Bet v 1 using a gnotobiotic mouse model. We showed that Lactobacillus (L.) rhamnosus LOCK0900, L. rhamnosus LOCK0908 and L. casei LOCK0919 are recognized via Toll-like receptor 2 (TLR2) and nucleotide-binding oligomerization domain-containing protein 2 (NOD2) receptors and stimulate bone marrow-derived dendritic cells to produce cytokines in species- and strain-dependent manners. Colonization of germ-free (GF) mice with a mixture of all three strains (Lmix) improved the intestinal barrier by strengthening the apical junctional complexes of enterocytes and restoring the structures of microfilaments extending into the terminal web. Mice colonized with Lmix and sensitized to the Bet v 1 allergen showed significantly lower levels of allergen-specific IgE, IgG1 and IgG2a and an elevated total IgA level in the sera and intestinal lavages as well as an increased transforming growth factor (TGF)-? level compared with the sensitized GF mice. Splenocytes and mesenteric lymph node cells from the Lmix-colonized mice showed the significant upregulation of TGF-? after in vitro stimulation with Bet v 1. Our results show that Lmix colonization improved the gut epithelial barrier and reduced allergic sensitization to Bet v 1. Furthermore, these findings were accompanied by the increased production of circulating and secretory IgA and the regulatory cytokine TGF-?. Thus, this mixture of three lactobacillus strains shows potential for use in the prevention of increased gut permeability and the onset of allergies in humans.
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Project description:BackgroundImmunoglobulin(Ig)E-associated allergies result from misguided immune responses against innocuous antigens. CD4+ T lymphocytes are critical for initiating and perpetuating that process, yet the crucial factors determining whether an individual becomes sensitized towards a given allergen remain largely unknown.ObjectiveTo determine the key factors for sensitization and allergy towards a given allergen.MethodsWe here created a novel human T cell receptor(TCR) and human leucocyte antigen (HLA)-DR1 (TCR-DR1) transgenic mouse model of asthma, based on the human-relevant major mugwort (Artemisia vulgaris) pollen allergen Art v 1 to examine the critical factors for sensitization and allergy upon natural allergen exposure via the airways in the absence of systemic priming and adjuvants.ResultsAcute allergen exposure led to IgE-independent airway hyperreactivity (AHR) and T helper(Th)2-prone lung inflammation in TCR-DR1, but not DR1, TCR or wildtype (WT) control mice, that was alleviated by prophylactic interleukin(IL)-2-αIL-2 mAb complex-induced expansion of Tregs. Chronic allergen exposure sensitized one third of single DR1 transgenic mice, however, without impacting on lung function. Similar treatment led to AHR and Th2-driven lung pathology in >90% of TCR-DR1 mice. Prophylactic and therapeutic expansion of Tregs with IL-2-αIL-2 mAb complexes blocked the generation and boosting of allergen-specific IgE associated with chronic allergen exposure.ConclusionsWe identify genetic restriction of allergen presentation as primary factor dictating allergic sensitization and disease against the major pollen allergen from the weed mugwort, which frequently causes sensitization and disease in humans. Furthermore, we demonstrate the importance of the balance between allergen-specific T effector and Treg cells for modulating allergic immune responses.
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