Synthesis of N-Glycans Implicated in Asthma and Allergy

Synthesis of N-glycans implicated in asthma and allergy

10.26686/wgtn.17009303 ◽

2021 ◽

Author(s):

◽

Gregory William Haslett

Keyword(s):

Immune Response ◽

Striking Similarity ◽

Glycan Structure ◽

Food Allergens ◽

T Helper ◽

Th2 Response ◽

Th2 Immune Response ◽

Asthma And Allergy ◽

Allergen Extracts ◽

The Relationship

Asthma and allergies affect a large number of people, with over 300 million people worldwide suffering from asthma alone. Although, on the ‟macroscopic‟ level, it is known how allergens trigger allergic reactions, it is not known how an allergen's ‟micro‟ structure causes such a profound allergic response in sensitised individuals. A review of inter-species carbohydrate motifs revealed a striking similarity between carbohydrate moieties (N-glycans) present on antigens derived from species known to give an allergic T helper (Th) 2 response in humans (such as pollen, schistosomes, and food allergens). Preliminary studies on mixtures of allergen extracts have suggested that these carbohydrate motifs (glycoproteins) bias the immune response to an allergic (Th2) response. This project presents work conducted towards the synthesis of three fragments of a larger N-glycan found on allergens. The synthesis of these N-glycans will allow the first detailed study regarding the relationship between N-glycan structure and Th2 bias to be performed and thereby aid in our understanding of the molecular triggers of asthma. Ultimately, this could lead to the elucidation of the mechanisms of the allergic Th2 immune response.

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Synthesis of N-Glycans Implicated in Asthma and Allergy

10.26686/wgtn.17011643.v1 ◽

2021 ◽

Author(s):

◽

Gregory William Haslett

Keyword(s):

Immune Response ◽

Striking Similarity ◽

Glycan Structure ◽

Food Allergens ◽

T Helper ◽

Th2 Response ◽

Th2 Immune Response ◽

Asthma And Allergy ◽

Allergen Extracts ◽

The Relationship

Asthma and allergies affect a large number of people, with over 300 million people worldwide suffering from asthma alone. Although, on the ‟macroscopic‟ level, it is known how allergens trigger allergic reactions, it is not known how an allergen's ‟micro‟ structure causes such a profound allergic response in sensitised individuals. A review of inter-species carbohydrate motifs revealed a striking similarity between carbohydrate moieties (N-glycans) present on antigens derived from species known to give an allergic T helper (Th) 2 response in humans (such as pollen, schistosomes, and food allergens). Preliminary studies on mixtures of allergen extracts have suggested that these carbohydrate motifs (glycoproteins) bias the immune response to an allergic (Th2) response. This project presents work conducted towards the synthesis of three fragments of a larger N-glycan found on allergens. The synthesis of these N-glycans will allow the first detailed study regarding the relationship between N-glycan structure and Th2 bias to be performed and thereby aid in our understanding of the molecular triggers of asthma. Ultimately, this could lead to the elucidation of the mechanisms of the allergic Th2 immune response.

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Synthesis of N-glycans implicated in asthma and allergy

10.26686/wgtn.17009303.v1 ◽

2021 ◽

Author(s):

◽

Gregory William Haslett

Keyword(s):

Immune Response ◽

Striking Similarity ◽

Glycan Structure ◽

Food Allergens ◽

T Helper ◽

Th2 Response ◽

Th2 Immune Response ◽

Asthma And Allergy ◽

Allergen Extracts ◽

The Relationship

Asthma and allergies affect a large number of people, with over 300 million people worldwide suffering from asthma alone. Although, on the ‟macroscopic‟ level, it is known how allergens trigger allergic reactions, it is not known how an allergen's ‟micro‟ structure causes such a profound allergic response in sensitised individuals. A review of inter-species carbohydrate motifs revealed a striking similarity between carbohydrate moieties (N-glycans) present on antigens derived from species known to give an allergic T helper (Th) 2 response in humans (such as pollen, schistosomes, and food allergens). Preliminary studies on mixtures of allergen extracts have suggested that these carbohydrate motifs (glycoproteins) bias the immune response to an allergic (Th2) response. This project presents work conducted towards the synthesis of three fragments of a larger N-glycan found on allergens. The synthesis of these N-glycans will allow the first detailed study regarding the relationship between N-glycan structure and Th2 bias to be performed and thereby aid in our understanding of the molecular triggers of asthma. Ultimately, this could lead to the elucidation of the mechanisms of the allergic Th2 immune response.

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T Helper Type 17 Immune Response Plays an Indispensable Role for Development of Iodine-Induced Autoimmune Thyroiditis in Nonobese Diabetic-H2h4 Mice

Endocrinology ◽

10.1210/en.2009-0434 ◽

2009 ◽

Vol 150 (11) ◽

pp. 5135-5142 ◽

Cited By ~ 51

Author(s):

Ichiro Horie ◽

Norio Abiru ◽

Yuji Nagayama ◽

Genpei Kuriya ◽

Ohki Saitoh ◽

...

Keyword(s):

Immune Response ◽

Autoimmune Thyroiditis ◽

Th17 Cells ◽

Intermediate Phenotype ◽

Lymphocyte Infiltration ◽

Wild Type ◽

T Helper ◽

Nonobese Diabetic ◽

Th2 Immune Response ◽

Helper Type

T helper type 1(Th1)/Th2 paradigm has been expanded by discovery of a novel effector T cell (Teff) subset, Th17 cells, which produce a proinflammatory cytokine IL-17. Th17 cells have recently been shown to play a major role in numerous autoimmune diseases that had previously been thought to be Th1-dominant diseases. We here studied the significance of Th17 cells in iodine-induced autoimmune thyroiditis in nonobese diabetic-H2h4 mice, a mouse model of Hashimoto’s thyroiditis in humans, which spontaneously develop antithyroglobulin autoantibodies and intrathyroidal lymphocyte infiltration when supplied with iodine in the drinking water. We observed increased numbers of Th1 and Th17 cells in spleen and accumulation of both types of Teff in the thyroid glands of iodine-fed wild-type mice, indicating that Th17 cells as well as Th1 cells constitute thyroid lesions. Furthermore, the incidence and severity of intrathyroidal lymphocyte infiltration, and the titers of antithyroglobulin autoantibodies were markedly reduced in iodine-treated IL-17−/− mice as compared with wild-type mice. Of interest, IL-17+/− mice showed an intermediate phenotype. Therefore, the present study, together with a previous report demonstrating the importance of Th1, not Th2, immune response for developing thyroiditis using mice deficient for interferon-γ or IL-4, clearly indicates that both Th1 and Th17 cells are critical Teff subsets for the pathogenesis of spontaneous autoimmune thyroiditis in nonobese diabetic-H2h4 mice.

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Is the Prevalence of Leishmania infantum Linked to Breeds in Dogs? Characterization of Seropositive Dogs in Ibiza

Animals ◽

10.3390/ani11092579 ◽

2021 ◽

Vol 11 (9) ◽

pp. 2579

Author(s):

Maria Edo ◽

Pablo Jesús Marín-García ◽

Lola Llobat

Keyword(s):

Immune Response ◽

Leishmania Infantum ◽

Protozoan Parasite ◽

Disease Stage ◽

Doberman Pinscher ◽

Th2 Immune Response ◽

Mediterranean Island ◽

Antibody Titers ◽

The Relationship

Leishmaniosis is an important zoonotic protozoan disease primarily spread to the Mediterranean region by Leishmania infantum, the predominant protozoan species, which accounts for the majority of cases. Development of disease depends on the immune response of the definitive host and, predictably, their genetic background. Recent studies have revealed breed-typical haplotypes that are susceptible to the spread of the protozoan parasite. The objective of this study was to analyze the prevalence of leishmaniosis on a Mediterranean island and determine the relationship between disease prevalence and breed. In addition, information on seropositive animals was recorded to characterize animals affected by the disease. To study the prevalence, a total of 3141 dogs were analyzed. Of these, the 149 infected animals were examined for age, sex, antibody titer, and disease stage. We observed a prevalence of 4.74%, which varied between breeds (p < 0.05). The Doberman Pinscher and Boxer breeds had the highest prevalence of leishmaniosis. Significant differences were observed between breeds with common ancestors, emphasizing the important genetic component. Finally, regarding the characterization of seropositive animals, the distribution is similar to other studies. We discovered a relationship (p < 0.05) between the number of antibody titers and the clinical disease stage, which was also present in Leishmania infantum, suggesting that the development of the disease depends on the humoral or Th2 immune response with ineffective antibodies.

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Periostin and Thymic Stromal Lymphopoietin—Potential Crosstalk in Obstructive Airway Diseases

Journal of Clinical Medicine ◽

10.3390/jcm9113667 ◽

2020 ◽

Vol 9 (11) ◽

pp. 3667

Author(s):

Patrycja Nejman-Gryz ◽

Katarzyna Górska ◽

Magdalena Paplińska-Goryca ◽

Małgorzata Proboszcz ◽

Rafał Krenke

Keyword(s):

Immune Response ◽

Mrna Level ◽

Thymic Stromal Lymphopoietin ◽

Atopic Asthma ◽

Chronic Obstructive ◽

Strong Positive Correlation ◽

Th2 Response ◽

Airway Diseases ◽

Th2 Immune Response ◽

Obstructive Airway Diseases

Periostin and thymic stromal lymphopoietin (TSLP) are newly described markers of obstructive airway diseases and the mechanism by which both markers participate in immune response remains poorly understood. The aim of our study was to determine periostin and TSLP concentration in serum and induced sputum (IS) in patients with atopic asthma, chronic obstructive pulmonary disease (COPD), and controls, as well as to evaluate the potential link between periostin, TSLP, and Th2 immune response. Serum and IS levels of periostin, TSLP, IL-4, and IL-13 were determined in 12 atopic asthmatics, 16 COPD sufferers, and 10 controls. We noticed a significantly higher IS periostin and TSLP concentration at protein and mRNA level in asthmatics compared to the two other groups; additionally, periostin and TSLP were correlated positively with IS eosinophil count. A strong positive correlation between IS periostin and TSLP protein levels (r = 0.96) as well as mRNA expression level (r = 0.95) was found in patients with asthma. The results of our study show that periostin and TSLP are associated with eosinophilic airway inflammation and seem to be important drivers of atopic asthma but not COPD pathobiology. Very strong correlations between local periostin, TSLP, eosinophils, and IL-4 in asthma point to the link between periostin–TSLP and Th2 response.

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Resistance to Haemonchus contortus in Corriedale sheep is associated to high parasite-specific IgA titer and a systemic Th2 immune response

Scientific Reports ◽

10.1038/s41598-019-55447-6 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Cecilia Escribano ◽

Anderson Saravia ◽

Monique Costa ◽

Daniel Castells ◽

Gabriel Ciappesoni ◽

...

Keyword(s):

Immune Response ◽

Haemonchus Contortus ◽

Adaptive Immune Response ◽

Gastrointestinal Nematode ◽

Economic Losses ◽

Th2 Response ◽

Th2 Immune Response ◽

Efficiency Of Selection ◽

High Parasite ◽

Selection Of

AbstractGastrointestinal nematode infections, including Haemonchus contortus, are one of the main causes of economic losses to ovine farmers worldwide. In order to contribute to the control of nematode infections and avoid parasite spreading we generated divergent resistant and susceptible sheep breeds and evaluated the adaptive immunity of these animals developed upon experimental infection against H. contortus. The selection of resistant or susceptible animals from the Corriedale Breed has been based on Expected Progeny Differences for faecal egg counts per gram. Furthermore, animals from the resistant Corriedale line were inseminated with imported semen from Australian Rylington Merino rams. Thus, the objective of this work was to analyze the adaptive immune response in both susceptible and resistant obtained lambs. Our results indicate that there is a potent parasite-specific local and systemic immune response in resistant animals and that although susceptible lambs can produce high levels of IgA antibodies during the infection, their antibody response is delayed which, together with an impaired specific-Th2 response, does not contribute to initial parasite elimination. Our results shed light into the immune mechanisms that mediate resistance to H. contortus and could constitute important assets to sheep farmers, not only as a means to detect resistance, but also to enhance the efficiency of selection in stud flocks.

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Both Free-Living and Parasitic Nematodes Induce a Characteristic Th2 Response That Is Dependent on the Presence of Intact Glycans

Infection and Immunity ◽

10.1128/iai.72.1.398-407.2004 ◽

2004 ◽

Vol 72 (1) ◽

pp. 398-407 ◽

Cited By ~ 87

Author(s):

Salah Tawill ◽

Laetitia Le Goff ◽

Fahimeda Ali ◽

Mark Blaxter ◽

Judith E. Allen

Keyword(s):

Immune Response ◽

Critical Role ◽

Interleukin 4 ◽

Parasitic Nematodes ◽

Mammalian Host ◽

Phylogenetic Distance ◽

Th2 Response ◽

Free Living ◽

Th2 Immune Response

ABSTRACT Infection with parasitic nematodes is characterized by the induction of a profound type 2 immune response. We have studied the role of glycans in the induction of the skewed type 2 response by antigens of the parasitic nematode Brugia malayi as well as the free-living nematode Caenorhabditis elegans. Lymph node cells from BALB/c mice immunized with soluble extracts of the two nematodes showed distinct antigen-specific proliferation and cytokine production; however, both nematodes induced antigen-specific interleukin 4 (IL-4) production, demonstrating that the induction of a biased type 2 response is not unique to parasitic nematodes. Sodium periodate-treated soluble extracts of both nematodes consistently induced significantly less IL-4 production than the respective mock-treated extracts, indicating that glycans play a critical role in the induction of the Th2 immune response by these nematodes. The glycan-dependent induction of the Th2-potentiating cytokine IL-4 occurs by 72 h postinoculation. Our data suggest that glycan determinants common to nematodes act as ligands, displaying distinct molecular patterns that trigger the immune system to launch a biased Th2 immune response upon exposure to these organisms or their products. Further, the similarity of our findings to those for Schistosoma mansoni egg antigen is striking considering the enormous phylogenetic distance between nematodes and trematodes. These data thus have important implications for how the mammalian host responds to widely divergent metazoan invaders and suggest that the powerful C. elegans model system can be used to address these questions.

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Selenium Status Alters the Immune Response and Expulsion of Adult Heligmosomoides bakeri Worms in Mice

Infection and Immunity ◽

10.1128/iai.01047-12 ◽

2013 ◽

Vol 81 (7) ◽

pp. 2546-2553 ◽

Cited By ~ 11

Author(s):

Allen D. Smith ◽

Lumei Cheung ◽

Ethiopia Beshah ◽

Terez Shea-Donohue ◽

Joseph F. Urban

Keyword(s):

Immune Response ◽

Small Intestine ◽

Metabolic Activity ◽

Surrounding Tissue ◽

Th2 Response ◽

Content Type ◽

Adequate Diet ◽

Th2 Immune Response ◽

Heligmosomoides Bakeri ◽

Deficient Mice

ABSTRACTHeligmosomoides bakeriis a nematode with parasitic development exclusively in the small intestine of infected mice that induces a potent STAT6-dependent Th2 immune response. We previously demonstrated that host protective expulsion of adultH. bakeriworms from a challenge infection was delayed in selenium (Se)-deficient mice. In order to explore mechanisms associated with the delayed expulsion, 3-week-old female BALB/c mice were placed on a torula yeast-based diet with or without 0.2 ppm Se, and after 5 weeks, they were inoculated withH. bakeriinfective third-stage larvae (L3s). Two weeks after inoculation, the mice were treated with an anthelmintic and then rested, reinoculated with L3s, and evaluated at various times after reinoculation. Analysis of gene expression in parasite-induced cysts and surrounding tissue isolated from the intestine of infected mice showed that the local-tissue Th2 response was decreased in Se-deficient mice compared to that in Se-adequate mice. In addition, adult worms recovered from Se-deficient mice had higher ATP levels than worms from Se-adequate mice, indicating greater metabolic activity in the face of a suboptimal Se-dependent local immune response. Notably, the process of worm expulsion was restored within 2 to 4 days after feeding a Se-adequate diet to Se-deficient mice. Expulsion was associated with an increased local expression of Th2-associated genes in the small intestine, intestinal glutathione peroxidase activity, secreted Relm-β protein, anti-H. bakeriIgG1 production, and reduced worm fecundity and ATP-dependent metabolic activity.

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The Role of Th17 Cells and IL-17 in Th2 Immune Responses of Allergic Conjunctivitis

Journal of Ophthalmology ◽

10.1155/2020/6917185 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9

Author(s):

Xiang-Tian Meng ◽

Yun-Yue Shi ◽

Hong Zhang ◽

Hong-Yan Zhou

Keyword(s):

Immune Response ◽

Immune Responses ◽

Lupus Erythematosus ◽

Th17 Cells ◽

Allergic Conjunctivitis ◽

Interleukin 17 ◽

Type I ◽

T Helper ◽

Th2 Immune Response

Allergic conjunctivitis (AC) is a common allergic disease that is often associated with the onset of rhinitis or asthma. The incidence of AC has increased significantly in recent years possibly due to air pollution and climate warming. AC seriously affects patients’ quality of life and work efficiency. Th (T-helper) 2 immune responses and type I hypersensitivity reactions are generally considered the basis of occurrence of AC. It has been found that new subpopulations of T-helper cells, Th17 cells that produce interleukin-17 (IL-17), play an important role in the Th2-mediated pathogenesis of conjunctivitis. Studies have shown that Th17 cells are involved in a variety of immune inflammation, including psoriasis, rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and asthma. However, the role of Th17 and IL-17 in AC is unclear. This paper will focus on how T-helper 17 cells and interleukin-17 are activated in the Th2 immune response of allergic conjunctivitis and how they promote the Th2 immune response of AC.

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