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1.
Sci Rep ; 12(1): 3329, 2022 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-35228630

RESUMO

Allergic sensitization is initiated by protein and epithelia interaction, although the molecular mechanisms leading this encounter toward an allergic phenotype remain unknown. Here, we apply the two-hit hypothesis of inflammatory diseases to the study of food allergy sensitization. First, we studied the effects of long-term depilation in mice by analyzing samples at different time points. Several weeks of depilation were needed until clear immunological changes were evidenced, starting with upregulation of NLRP3 protein levels, which was followed by overexpression of Il1b and Il18 transcripts. Secondly, we assessed the effects of allergen addition (in this case, Pru p 3 in complex with its natural lipid ligand) over depilated skin. Systemic sensitization was evaluated by intraperitoneal provocation with Pru p 3 and measure of body temperature. Anaphylaxis was achieved, but only in mice sensitized with Prup3_complex and not treated with the NLRP3 inhibitor MCC950, thus demonstrating the importance of both hits (depilation + allergen addition) in the consecution of the allergic phenotype. In addition, allergen encounter (but not depilation) promoted skin remodeling, as well as CD45+ infiltration not only in the sensitized area (the skin), but across several mucosal tissues (skin, lungs, and gut), furtherly validating the systemization of the response. Finally, a low-scale study with human ILC2s is reported, where we demonstrate that Prup3_complex can induce their phenotype switch (↑CD86, ↑S1P1) when cultured in vitro, although more data is needed to understand the implications of these changes in food allergy development.


Assuntos
Antígenos de Plantas , Hipersensibilidade Alimentar , Imunoglobulina E , Proteína 3 que Contém Domínio de Pirina da Família NLR , Alérgenos/imunologia , Animais , Antígenos de Plantas/administração & dosagem , Antígenos de Plantas/imunologia , Modelos Animais de Doenças , Hipersensibilidade Alimentar/imunologia , Furanos/farmacologia , Imunidade Inata , Imunoglobulina E/imunologia , Indenos/farmacologia , Linfócitos/imunologia , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Proteínas de Plantas/administração & dosagem , Proteínas de Plantas/imunologia , Sulfonamidas/farmacologia
2.
Sci Rep ; 12(1): 2797, 2022 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-35181694

RESUMO

To investigate food allergy-tolerance mechanisms induced through allergen-specific immunotherapy we used RNA-Sequencing to measure gene expression in lymph-node-derived dendritic cells from Pru p 3-anaphylactic mice after immunotherapy with glycodendropeptides at 2 nM and 5 nM, leading to permanent tolerance and short-term desensitization, respectively. Gene expression was also measured in mice receiving no immunotherapy (anaphylaxis); and in which anaphylaxis could never occur (antigen-only). Compared to anaphylaxis, the antigen-only group showed the greatest number of expression-changes (411), followed by tolerant (186) and desensitized (119). Only 29 genes changed in all groups, including Il12b, Cebpb and Ifngr1. The desensitized group showed enrichment for genes related to chronic inflammatory response, secretory granule, and regulation of interleukin-12 production; the tolerant group showed genes related to cytokine receptor activity and glucocorticoid receptor binding, suggesting distinct pathways for similar outcomes. We identified genes and processes potentially involved in the restoration of long-term tolerance via allergen-specific immunotherapy, representing potential prognostic biomarkers.


Assuntos
Proteína beta Intensificadora de Ligação a CCAAT/genética , Dessensibilização Imunológica , Tolerância Imunológica/genética , Subunidade p40 da Interleucina-12/genética , Receptores de Interferon/genética , Alérgenos/imunologia , Alérgenos/farmacologia , Anafilaxia/genética , Anafilaxia/imunologia , Animais , Antígenos de Plantas/farmacologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Modelos Animais de Doenças , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/imunologia , Regulação da Expressão Gênica/efeitos dos fármacos , Glicopeptídeos/farmacologia , Humanos , Interleucina-12/genética , Linfonodos/imunologia , Camundongos , Proteínas de Plantas/farmacologia , RNA-Seq
3.
J Clin Lab Anal ; 36(2): e24222, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34994992

RESUMO

INTRODUCTION: Multiple allergen simultaneous test (MAST) is widely used as a screening tool for allergic diseases and has the advantage of providing specific IgE (sIgE) results for various allergens in semiquantitative class. We have continuously conducted external quality assessment (EQA) since 2012 for clinical laboratories performing MAST using AdvanSure allergy screen test (LG CHEM, Korea). This study provides an account of the EQA experience. METHODS: Samples were prepared using pooled sera collected from patients with suspected allergic disease and sent to each laboratory twice a year. Each round included 4-6 serum samples with sIgE for 10-20 inhaled or food allergens. The acceptable class value was the most frequently reported MAST class ±1 titer that exceeded 80% of the total laboratory results. RESULTS: The average number of participating laboratories was 76 (49-90) and the average response rate was 97.3% during the entire survey period. The acceptable rates were consistently high at 97.7% ± 3.7%. Of the total 537 trials, 18 trials (3.4%) were regarded as nonconsensus results, in which acceptable answers did not exceed 80%. For unacceptable results, the false-negative rate (1.5% ± 2.8%) was higher than the false-positive rate (0.8% ± 2.7%) (p < 0.001). MAST class results were correlated with quantitative IgE results by ImmunoCAP (Spearman's correlation coefficient of 0.682 (p < 0.001) and gamma index of 0.777 (p < 0.001). CONCLUSION: Although EQA for MAST showed a high level of acceptable answer, some allergen assays require harmonization. Continuous performance of systematic EQA is needed to improve the accuracy of sIgE assays and quality control in clinical laboratories.


Assuntos
Alérgenos/sangue , Hipersensibilidade/diagnóstico , Imunoglobulina E/sangue , Garantia da Qualidade dos Cuidados de Saúde , Técnicas de Laboratório Clínico , Erros de Diagnóstico/estatística & dados numéricos , Hipersensibilidade Alimentar/diagnóstico , Hipersensibilidade Alimentar/imunologia , Humanos , Hipersensibilidade/imunologia , Medições Luminescentes , República da Coreia
4.
J Immunol ; 208(2): 267-277, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-35017216

RESUMO

Alpha-gal syndrome (AGS) describes a collection of symptoms associated with IgE-mediated hypersensitivity responses to the glycan galactose-alpha-1,3-galactose (alpha-gal). Individuals with AGS develop delayed hypersensitivity reactions, with symptoms occurring >2 h after consuming mammalian ("red") meat and other mammal-derived food products. The mechanisms of pathogenesis driving this paradigm-breaking food allergy are not fully understood. We review the role of tick bites in the development of alpha-gal-specific IgE and highlight innate and adaptive immune cells possibly involved in alpha-gal sensitization. We discuss the impact of alpha-gal glycosylation on digestion and metabolism of alpha-gal glycolipids and glycoproteins, and the implications for basophil and mast cell activation and mediator release that generate allergic symptoms in AGS.


Assuntos
Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/fisiopatologia , Imunoglobulina E/imunologia , Picadas de Carrapatos/fisiopatologia , Animais , Bactérias/imunologia , Modelos Animais de Doenças , Glicolipídeos/metabolismo , Glicoproteínas/metabolismo , Humanos , Hipersensibilidade Imediata/imunologia , Hipersensibilidade Imediata/patologia , Linfócitos/imunologia , Camundongos , Carne Vermelha/efeitos adversos , Picadas de Carrapatos/microbiologia
5.
Arterioscler Thromb Vasc Biol ; 42(3): 352-361, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35045730

RESUMO

BACKGROUND: Treating known risk factors for coronary artery disease (CAD) has substantially reduced CAD morbidity and mortality. However, a significant burden of CAD remains unexplained. Immunoglobulin E sensitization to mammalian oligosaccharide galactose-α-1,3-galactose (α-Gal) was recently associated with CAD in a small observational study. We sought to confirm that α-Gal sensitization is associated with CAD burden, in particular noncalcified plaque. Additionally, we sort to assess whether that α-Gal sensitization is associated with ST-segment-elevated myocardial infarction (STEMI) Methods: We performed a cross-sectional analysis of participants enrolled in the BioHEART cohort study. We measured α-Gal specific-immunoglobulin E antibodies in serum of 1056 patients referred for CT coronary angiography for suspected CAD and 100 selected patients presenting with STEMI, enriched for patients without standard modifiable risk factors. CT coronary angiograms were assessed using coronary artery calcium scores and segmental plaque scores. RESULTS: α-Gal sensitization was associated with presence of noncalcified plaque (odds ratio, 1.62 [95% CI, 1.04-2.53], P=0.03) and obstructive CAD (odds ratio, 2.05 [95% CI, 1.29-3.25], P=0.002), independent of age, sex, and traditional risk factors. The α-Gal sensitization rate was 12.8-fold higher in patients with STEMI compared with matched healthy controls and 2.2-fold higher in the patients with STEMI compared with matched stable CAD patients (17% versus 1.3%, P=0.01 and 20% versus 9%, P=0.03, respectively). CONCLUSIONS: α-Gal sensitization is independently associated with noncalcified plaque burden and obstructive CAD and occurs at higher frequency in patients with STEMI than those with stable or no CAD. These findings may have implications for individuals exposed to ticks, as well as public health policy. Registration: URL: https://www.anzctr.org.au; Unique identifier: ACTRN12618001322224.


Assuntos
Doença da Artéria Coronariana/etiologia , Doença da Artéria Coronariana/imunologia , Hipersensibilidade Alimentar/complicações , Placa Aterosclerótica/etiologia , Placa Aterosclerótica/imunologia , Infarto do Miocárdio com Supradesnível do Segmento ST/etiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/imunologia , Idoso , Animais , Estudos de Coortes , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Estudos Transversais , Dissacarídeos/imunologia , Feminino , Hipersensibilidade Alimentar/imunologia , Humanos , Imunoglobulina E/sangue , Imunoglobulina E/imunologia , Masculino , Pessoa de Meia-Idade , Placa Aterosclerótica/diagnóstico por imagem , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença , Calcificação Vascular/diagnóstico por imagem
6.
Oxid Med Cell Longev ; 2022: 3605977, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35096267

RESUMO

Allergen-specific immunotherapy (SIT) is the mainstay in the treatment of allergic diseases; its therapeutic efficacy is to be improved. Bacterial flagellin (FGN) has immune regulatory functions. This study investigates the role of FGN in promoting immunotherapy efficacy through modulating oxidative stress in regulatory B cells (Bregs). Blood samples were collected from patients with food allergy (FA) and healthy control (HC) subjects. CD19+ CD5+ Bregs were purified from blood samples by flow cytometry cell sorting. A murine FA model was developed with ovalbumin as the specific antigen. The results showed that peripheral Bregs from FA patients showed lower TLR5-related signals and higher apoptotic activities. The peripheral Breg frequency was negatively correlated with serum FGN levels in FA patients. Exposure to a specific antigen in culture induced antigen-specific Breg apoptosis that was counteracted by the presence of FGN. FGN diminished specific antigen-induced oxidative stress in Bregs. The STAT3/MAPKp38/NF-κB signal pathway was involved in the FGN/TLR5 signal-promoted superoxide dismutase expression in Bregs. Administration of FGN promotes the SIT efficacy in suppressing experimental FA. In summary, administration of FGN promotes SIT efficacy on FA, suggesting that the combination of FGN and SIT can be a novel therapy that has the translational potential to be employed in the treatment of allergic diseases.


Assuntos
Linfócitos B Reguladores/imunologia , Hipersensibilidade Alimentar/imunologia , Imunoterapia/métodos , Estresse Oxidativo/fisiologia , Adolescente , Adulto , Criança , Feminino , Humanos , Masculino , Adulto Jovem
7.
Regul Toxicol Pharmacol ; 129: 105112, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34973388

RESUMO

Some proteins, including enzymes, can induce allergic sensitization of various types, including allergic sensitization of the respiratory tract. There is now an increased understanding of the role that the skin plays in the development of IgE-mediated allergy and this prompts the question whether topical exposure to enzymes used widely in consumer cleaning products could result in allergic sensitization. Here, the evidence that proteins can interact with the skin immune system and the way they do so is reviewed, together with a consideration of the experience gained over decades of the use of enzymes in laundry and cleaning products. The conclusion drawn is that although transcutaneous sensitization to proteins can occur (typically through compromised skin) resulting in IgE antibody-mediated allergy, in practice such skin contact with enzymes used in laundry and cleaning products does not appear to pose a significant risk of allergic disease. Further, the evidence summarized in this publication support the view that proteins do not pose a risk of allergic contact dermatitis.


Assuntos
Detergentes/farmacologia , Enzimas/imunologia , Hipersensibilidade/etiologia , Hipersensibilidade/imunologia , Pele/imunologia , Alérgenos/imunologia , Dermatite Alérgica de Contato/etiologia , Dermatite Alérgica de Contato/imunologia , Hipersensibilidade Alimentar/etiologia , Hipersensibilidade Alimentar/imunologia , Humanos , Peso Molecular , Sistema Respiratório/imunologia
8.
Nutrients ; 14(2)2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35057553

RESUMO

As of late, evidence has been emerging that the Maillard reaction (MR, also referred to as glycation) affects the structure and function of food proteins. MR induces the conformational and chemical modification of food proteins, not only on the level of IgG/IgE recognition, but also by increasing the interaction and recognition of these modified proteins by antigen-presenting cells (APCs). This affects their biological properties, including digestibility, bioavailability, immunogenicity, and ultimately their allergenicity. APCs possess various receptors that recognize glycation structures, which include receptor for advanced glycation end products (RAGE), scavenger receptors (SRs), galectin-3 and CD36. Through these receptors, glycation structures may influence the recognition, uptake and antigen-processing of food allergens by dendritic cells (DCs) and monocytes. This may lead to enhanced cytokine production and maturation of DCs, and may also induce adaptive immune responses to the antigens/allergens as a result of antigen uptake, processing and presentation to T cells. Here, we aim to review the current literature on the immunogenicity of AGEs originating from food (exogenous or dietary AGEs) in relation to AGEs that are formed within the body (endogenous AGEs), their interactions with receptors present on immune cells, and their effects on the activation of the innate as well as the adaptive immune system. Finally, we review the clinical relevance of AGEs in food allergies.


Assuntos
Imunidade Adaptativa , Hipersensibilidade Alimentar/imunologia , Produtos Finais de Glicação Avançada/imunologia , Imunidade Inata , Alérgenos/imunologia , Apresentação do Antígeno/imunologia , Células Apresentadoras de Antígenos/imunologia , Células Dendríticas/imunologia , Dieta/métodos , Alimentos , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Reação de Maillard , Receptor para Produtos Finais de Glicação Avançada/imunologia , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Linfócitos T/imunologia
9.
Nutrients ; 14(2)2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35057567

RESUMO

Food protein-induced enterocolitis syndrome (FPIES) is a non-immunoglobin E-mediated food hypersensitivity disorder. However, little is known about the clinical features of FPIES in patients with Down syndrome (DS). Medical records of children with DS diagnosed at our hospital between 2000 and 2019 were retrospectively reviewed. Among the 43 children with DS, five (11.6%) were diagnosed with FPIES; all cases were severe. In the FPIES group, the median age at onset and tolerance was 84 days and 37.5 months, respectively. Causative foods were cow's milk formula and wheat. The surgical history of colostomy was significantly higher in the FPIES group than in the non-FPIES group. A colostomy was performed in two children in the FPIES group, both of whom had the most severe symptoms of FPIES, including severe dehydration and metabolic acidosis. The surgical history of colostomy and postoperative nutrition of formula milk feeding may have led to the onset of FPIES. Therefore, an amino acid-based formula should be considered for children who undergo gastrointestinal surgeries, especially colostomy in neonates or early infants. When an acute gastrointestinal disease is suspected in children with DS, FPIES should be considered. This may prevent unnecessary tests and invasive treatments.


Assuntos
Síndrome de Down/imunologia , Enterocolite/imunologia , Hipersensibilidade Alimentar/imunologia , Alérgenos/imunologia , Animais , Estudos de Casos e Controles , Bovinos , Pré-Escolar , Colostomia/efeitos adversos , Proteínas na Dieta/imunologia , Enterocolite/diagnóstico , Enterocolite/epidemiologia , Humanos , Imunoglobulina E/sangue , Lactente , Fórmulas Infantis/efeitos adversos , Leite/imunologia , Complicações Pós-Operatórias/imunologia , Estudos Retrospectivos , Síndrome , Hipersensibilidade a Trigo/imunologia
13.
J Allergy Clin Immunol ; 147(4): 1154-1163, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33217410

RESUMO

Allergies to peanuts, tree nuts, and sesame seeds are among the most important food-related causes of anaphylaxis. Important clinical questions include: Why is there a variable occurrence of coallergy among these foods and Is this immunologically mediated? The clinical and immunologic data summarized here suggest an immunologic basis for these coallergies that is based on similarities among the 2S albumins. Data from component resolved diagnostics have highlighted the relationship between IgE binding to these allergens and the presence of IgE-mediated food allergy. Furthermore, in vitro and in vivo experiments provide strong evidence that the 2S albumins are the most important allergens in peanuts for inducing an allergic effector response. Although the 2S albumins are diverse, they have a common disulfide-linked core with similar physicochemical properties that make them prime candidates to explain much of the observed coallergy among peanuts, tree nuts, and sesame seeds. The well-established frequency of cashew and pistachio nut coallergy (64%-100%) highlights how the structural similarities among their 2S albumins may account for observed clinical cross-reactivity. A complete understanding of the physicochemical properties of the 2S albumins in peanuts, tree nuts, and sesame seeds will enhance our ability to diagnose, treat, and ultimately prevent these allergies.


Assuntos
Albuminas 2S de Plantas/imunologia , Alérgenos/imunologia , Antígenos de Plantas/imunologia , Arachis/imunologia , Hipersensibilidade Alimentar/imunologia , Nozes/imunologia , Sementes/imunologia , Animais , Reações Cruzadas , Humanos , Imunoglobulina E/metabolismo , Sesamum/imunologia
14.
Int J Mol Sci ; 22(24)2021 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-34947981

RESUMO

Food hypersensitivity is a group of diseases arising from a specific immune response that reproduces on exposure to a given food. The current understanding of molecular mechanisms and immunopathology of non-IgE-mediated/mixed food hypersensitivity, e.g., eosinophilic esophagitis, contains many gaps in knowledge. This review aims to provide a modern classification and identify the primary diseases of non-IgE-mediated/mixed food hypersensitivity reactions, delineate the distinctive molecular features, and discuss recent findings in the immunopathology of eosinophilic esophagitis that may become a basis to develop valid biomarkers and novel therapies for this disease. Eosinophilic esophagitis is a recently recognized allergic-mediated disease with eosinophil-predominant esophagus inflammation. Its pathogenesis is a complicated network of interactions and signaling between epithelial, mesenchymal, and immune cells on molecular and intercellular levels. Alterations produced by overactivation of some cytokine signaling pathways, e.g., IL-13 or thymic stromal lymphopoietin (TSLP), were evolved and observed in this review from the viewpoints of molecular, genetic, epigenetic, and transcriptomic changes. Despite substantial experimental data, the reliable and representative mechanism of eosinophilic esophagitis pathogenesis has yet to show itself. So, the place of esophagitis between mixed and non-IgE-mediated allergic disorders and between eosinophilic gastrointestinal disorders currently seems vague and unclear.


Assuntos
Esofagite Eosinofílica/imunologia , Hipersensibilidade Alimentar/imunologia , Transdução de Sinais , Citocinas/metabolismo , Esofagite Eosinofílica/genética , Epigênese Genética , Hipersensibilidade Alimentar/genética , Regulação da Expressão Gênica , Humanos , Interleucina-3/metabolismo
15.
Nutrients ; 13(12)2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34959895

RESUMO

Food allergy (FA) is an increasing problem worldwide and, over recent years, its prevalence is rising in developed countries. Nowadays, the immunological and cellular processes that occur in the allergic reactions are not fully understood, which hampers the development of in vitro diagnostic tools and further treatment options. Moreover, allergic diseases could be reinforced by environmental exposure and genetic modifications. Gene expression can be controlled by different epigenetic mechanisms like DNA methylation, histone modifications, and microRNAs. In addition, several environmental factors such as dietary components (vitamin D, butyrate, folic acid) are able to regulate this epigenetic mechanism. All these factors produce modifications in immune genes that could alter the development and function of immune cells, and therefore the etiology of the disease. Furthermore, these epigenetic mechanisms have also an influence on immunomodulation, which could explain sustained responsiveness or unresponsiveness during immunotherapy due to epigenetic modifications in key genes that induce tolerance in several FA. Thus, in this review we focus on the different epigenetic mechanisms that occur in FA and on the influence of several dietary components in these gene modifications.


Assuntos
Epigênese Genética , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/imunologia , Butiratos , Metilação de DNA , Ácido Fólico , Código das Histonas , Humanos , Tolerância Imunológica/genética , Tolerância Imunológica/imunologia , MicroRNAs , Linfócitos T/imunologia , Vitamina D
16.
Front Immunol ; 12: 737658, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721398

RESUMO

Gut-microbiota dysbiosis links to allergic diseases. The mechanism of the exacerbation of food allergy caused by gut-microbiota dysbiosis remains unknown. Regulation of retinoic acid receptor alpha (RARα) signaling is critical for gut immune homeostasis. Here we clarified that RARα in dendritic cells (DCs) promotes Th2 cell differentiation. Antibiotics treatment stimulates retinoic acid signaling in mucosal DCs. We found microbiota metabolites short-chain fatty acids (SCFAs) maintain IGF-1 levels in serum and mesenteric lymph nodes. The IGF-1/Akt pathway is essential for regulating the transcription of genes targeted by RARα. And RARα in DCs affects type I interferon (IFN-I) responses through regulating transcription of IFN-α. Our study identifies SCFAs crosstalk with RARα in dendritic cells as a critical modulator that plays a core role in promoting Th2 cells differentiation at a state of modified/disturbed microbiome.


Assuntos
Bactérias/metabolismo , Células Dendríticas/metabolismo , Ácidos Graxos Voláteis/metabolismo , Hipersensibilidade Alimentar/metabolismo , Microbioma Gastrointestinal , Receptor alfa de Ácido Retinoico/metabolismo , Tretinoína/metabolismo , Animais , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Células Cultivadas , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Modelos Animais de Doenças , Disbiose , Ácidos Graxos Voláteis/farmacologia , Hipersensibilidade Alimentar/genética , Hipersensibilidade Alimentar/imunologia , Hipersensibilidade Alimentar/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Fator de Crescimento Insulin-Like I/metabolismo , Interferon Tipo I/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor alfa de Ácido Retinoico/genética , Transdução de Sinais , Células Th2/imunologia , Células Th2/metabolismo
17.
ACS Chem Biol ; 16(11): 2651-2664, 2021 11 19.
Artigo em Inglês | MEDLINE | ID: mdl-34761908

RESUMO

Covalent conjugation of allergens to toll-like receptor (TLR) agonists appears to be a powerful strategy for the development of safety compounds for allergen-specific immunomodulatory response toward tolerance in allergy. In this work, we have synthesized two family of ligands, an 8-oxoadenine derivative as a ligand for TLR7 and a pyrimido[5,4-b]indole as a ligand for TLR4, both conjugated with a T-cell peptide of Pru p 3 allergen, the lipid transfer protein (LTP) responsible for LTP-dependent food allergy. These conjugates interact with dendritic cells, inducing their specific maturation, T-cell proliferation, and cytokine production in peach allergic patients. Moreover, they increased the Treg-cell frequencies in these patients and could induce the IL-10 production. These outcomes were remarkable in the case of the TLR7 ligand conjugated with Pru p 3, opening the door for the potential application of these allergen-adjuvant systems in food allergy immunotherapy.


Assuntos
Hipersensibilidade Alimentar/metabolismo , Imunomodulação , Peptídeos/metabolismo , Receptor 4 Toll-Like/metabolismo , Receptor 7 Toll-Like/metabolismo , Alérgenos/metabolismo , Proteínas de Transporte/metabolismo , Proliferação de Células , Citocinas/biossíntese , Hipersensibilidade Alimentar/imunologia , Humanos , Ligantes , Linfócitos T/citologia , Linfócitos T/imunologia , Receptor 4 Toll-Like/agonistas , Receptor 7 Toll-Like/agonistas
18.
Nutrients ; 13(11)2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34835940

RESUMO

Mounting evidence demonstrates that a high-salt diet (HSD) not only affects hemodynamic changes but also disrupts immune homeostasis. The T helper 17 (Th17) and regulatory T cells (Tregs) are susceptible to hypersalinity. However, research on the influence of sodium on Th2-mediated food allergies remains scarce. We aimed to investigate the effect of dietary sodium on the immune response to food allergies. Mice maintained on an HSD (4% NaCl), low-salt diet (LSD; 0.4% NaCl), or control diet (CTRL; 1.0% NaCl) were orally sensitized with ovalbumin (OVA) and a cholera toxin (CT) adjuvant, and then subjected to an intragastric OVA challenge. OVA-specific immunoglobulin G (IgG), IgG1, IgG2a, and IgE antibodies were significantly higher in the HSD group than in the CTRL group (p < 0.001, p < 0.05, p < 0.01, and p < 0.05, respectively). Mice on HSD had significantly higher interleukin (IL)-4 levels than the CTRL group (p < 0.01). The IL-10 levels were significantly lower in the HSD group than in the CTRL group (p < 0.05). The serum levels of interferon-γ (IFN-γ), sodium, and chloride did not differ among the three groups. This study indicates that excessive salt intake promotes Th2 responses in a mouse model of food allergy.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal/imunologia , Dieta/efeitos adversos , Hipersensibilidade Alimentar/imunologia , Tolerância ao Sal/imunologia , Sódio na Dieta/imunologia , Animais , Dieta/métodos , Dieta Hipossódica/métodos , Modelos Animais de Doenças , Hipersensibilidade Alimentar/etiologia , Imunidade , Camundongos , Ovalbumina/imunologia , Sódio na Dieta/administração & dosagem , Linfócitos T Reguladores/imunologia , Células Th2/imunologia
19.
Nat Commun ; 12(1): 5958, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645820

RESUMO

Understanding the functional potential of the gut microbiome is of primary importance for the design of innovative strategies for allergy treatment and prevention. Here we report the gut microbiome features of 90 children affected by food (FA) or respiratory (RA) allergies and 30 age-matched, healthy controls (CT). We identify specific microbial signatures in the gut microbiome of allergic children, such as higher abundance of Ruminococcus gnavus and Faecalibacterium prausnitzii, and a depletion of Bifidobacterium longum, Bacteroides dorei, B. vulgatus and fiber-degrading taxa. The metagenome of allergic children shows a pro-inflammatory potential, with an enrichment of genes involved in the production of bacterial lipo-polysaccharides and urease. We demonstrate that specific gut microbiome signatures at baseline can be predictable of immune tolerance acquisition. Finally, a strain-level selection occurring in the gut microbiome of allergic subjects is identified. R. gnavus strains enriched in FA and RA showed lower ability to degrade fiber, and genes involved in the production of a pro-inflammatory polysaccharide. We demonstrate that a gut microbiome dysbiosis occurs in allergic children, with R. gnavus emerging as a main player in pediatric allergy. These findings may open new strategies in the development of innovative preventive and therapeutic approaches. Trial: NCT04750980.


Assuntos
Alérgenos/imunologia , Hipersensibilidade Alimentar/microbiologia , Microbioma Gastrointestinal/imunologia , Tolerância Imunológica , Hipersensibilidade Respiratória/microbiologia , Alérgenos/efeitos adversos , Animais , Bacteroides/isolamento & purificação , Bacteroides/metabolismo , Bifidobacterium longum/isolamento & purificação , Bifidobacterium longum/metabolismo , Estudos de Casos e Controles , Criança , Pré-Escolar , Clostridiales/isolamento & purificação , Clostridiales/metabolismo , Alérgenos Animais/efeitos adversos , Alérgenos Animais/imunologia , Ovos/efeitos adversos , Faecalibacterium prausnitzii/isolamento & purificação , Faecalibacterium prausnitzii/metabolismo , Feminino , Hipersensibilidade Alimentar/etiologia , Hipersensibilidade Alimentar/imunologia , Humanos , Lipopolissacarídeos/biossíntese , Masculino , Leite/efeitos adversos , Leite/imunologia , Nozes/efeitos adversos , Nozes/imunologia , Pólen/química , Pólen/imunologia , Prunus persica/química , Prunus persica/imunologia , Pyroglyphidae/química , Pyroglyphidae/imunologia , Hipersensibilidade Respiratória/etiologia , Hipersensibilidade Respiratória/imunologia , Urease/biossíntese
20.
Nutrients ; 13(10)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34684397

RESUMO

Crustacean allergy, especially to shrimp, is the most predominant cause of seafood allergy. However, due to the high flexibility of immunoglobulin E (IgE), its three-dimensional structure remains unsolved, and the molecular mechanism of shrimp allergen recognition is unknown. Here a chimeric IgE was built in silico, and its variable region in the light chain was replaced with sequences derived from shrimp tropomyosin (TM)-allergic patients. A variety of allergenic peptides from the Chinese shrimp TM were built, treated with heating, and subjected to IgE binding in silico. Amino acid analysis shows that the amino acid residue conservation in shrimp TM contributes to eliciting an IgE-mediated immune response. In the shrimp-allergic IgE, Glu98 in the light chain and other critical residues that recognize allergens from shrimp are implicated in the molecular basis of IgE-mediated shrimp allergy. Heat treatment could alter the conformations of TM allergenic peptides, impact their intramolecular hydrogen bonding, and subsequently decrease the binding between these peptides and IgE. We found Glu98 as the characteristic amino acid residue in the light chain of IgE to recognize general shrimp-allergic sequences, and heat-induced conformational change generally desensitizes shrimp allergens.


Assuntos
Alérgenos/imunologia , Hipersensibilidade Alimentar/imunologia , Imunoglobulina E/imunologia , Penaeidae/imunologia , Frutos do Mar , Tropomiosina/química , Tropomiosina/imunologia , Alérgenos/química , Sequência de Aminoácidos , Animais , Epitopos/imunologia , Hipersensibilidade Alimentar/terapia , Temperatura Alta , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Imunoglobulina E/química , Imunoglobulina E/metabolismo , Modelos Moleculares , Simulação de Dinâmica Molecular , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/metabolismo , Conformação Proteica , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/imunologia , Alinhamento de Sequência , Tropomiosina/metabolismo
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