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

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.

Download Full-text

An explicit immunogenetic model of gastrointestinal nematode infection in sheep

Journal of The Royal Society Interface ◽

10.1098/rsif.2014.0416 ◽

2014 ◽

Vol 11 (99) ◽

pp. 20140416 ◽

Cited By ~ 11

Author(s):

Joaquín Prada Jiménez de Cisneros ◽

Michael J. Stear ◽

Colette Mair ◽

Darran Singleton ◽

Thorsten Stefan ◽

...

Keyword(s):

Immune Response ◽

Immune Responses ◽

Selective Breeding ◽

Adaptive Immune Response ◽

Infection Intensity ◽

Gastrointestinal Nematode ◽

High Plasma ◽

Gastrointestinal Nematodes ◽

Development Of Resistance ◽

Infection Dynamics

Gastrointestinal nematodes are a global cause of disease and death in humans, wildlife and livestock. Livestock infection has historically been controlled with anthelmintic drugs, but the development of resistance means that alternative controls are needed. The most promising alternatives are vaccination, nutritional supplementation and selective breeding, all of which act by enhancing the immune response. Currently, control planning is hampered by reliance on the faecal egg count (FEC), which suffers from low accuracy and a nonlinear and indirect relationship with infection intensity and host immune responses. We address this gap by using extensive parasitological, immunological and genetic data on the sheep– Teladorsagia circumcincta interaction to create an immunologically explicit model of infection dynamics in a sheep flock that links host genetic variation with variation in the two key immune responses to predict the observed parasitological measures. Using our model, we show that the immune responses are highly heritable and by comparing selective breeding based on low FECs versus high plasma IgA responses, we show that the immune markers are a much improved measure of host resistance. In summary, we have created a model of host–parasite infections that explicitly captures the development of the adaptive immune response and show that by integrating genetic, immunological and parasitological understanding we can identify new immune-based markers for diagnosis and control.

Download Full-text

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.

Download Full-text

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.

Download Full-text

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.

Download Full-text

Resveratrol, EGCG and Vitamins Modulate Activated T Lymphocytes

Molecules ◽

10.3390/molecules26185600 ◽

2021 ◽

Vol 26 (18) ◽

pp. 5600

Author(s):

Joseph Schwager ◽

Nicole Seifert ◽

Albine Bompard ◽

Daniel Raederstorff ◽

Igor Bendik

Keyword(s):

Gene Expression ◽

Immune Response ◽

T Lymphocytes ◽

T Lymphocyte ◽

Adaptive Immune Response ◽

Marginal Effect ◽

Th2 Response ◽

T Lymphocyte Subsets ◽

Adaptive Immune ◽

T Lymphocyte Proliferation

Vitamins and bioactives, which are constituents of the food chain, modulate T lymphocyte proliferation and differentiation, antibody production, and prevent inflammation and autoimmunity. We investigated the effects of vitamins (vitamin A (VA), D (VD), E (VE)) and bioactives (i.e., resveratrol (Res), epigallocatechin-3-gallate (EGCG)) on the adaptive immune response, as well as their synergistic or antagonistic interactions. Freshly isolated T lymphocytes from healthy individuals were activated with anti-CD3/CD28 antibodies for 4–5 days in the presence of bioactives and were analyzed by cytofluorometry. Interleukins, cytokines, and chemokines were measured by multiple ELISA. Gene expression was measured by quantitative RT-PCR. Res and EGCG increased CD4 surface intensity. EGCG led to an increased proportion of CD8+ lymphocytes. Anti-CD3/CD28 activation induced exuberant secretion of interleukins and cytokines by T lymphocyte subsets. VD strongly enhanced Th2 cytokines (e.g., IL-5, IL-13), whereas Res and EGCG favored secretion of Th1 cytokines (e.g., IL-2, INF-γ). Res and VD mutually influenced cytokine production, but VD dominated the cytokine secretion pattern. The substances changed gene expression of interleukins and cytokines in a similar way as they did secretion. Collectively, VD strongly modulated cytokine and interleukin production and favored Th2 functions. Resveratrol and EGCG promoted the Th1 response. VA and VE had only a marginal effect, but they altered both Th1 and Th2 response. In vivo, bioactives might therefore interact with vitamins and support the outcome and extent of the adaptive immune response.

Download Full-text

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.

Download Full-text

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.

Download Full-text

Prior Toxoplasma Gondii Infection Ameliorates Liver Fibrosis Induced by Schistosoma Japonicum through Inhibiting Th2 Response and Improving Balance of Intestinal Flora in Mice

International Journal of Molecular Sciences ◽

10.3390/ijms21082711 ◽

2020 ◽

Vol 21 (8) ◽

pp. 2711 ◽

Cited By ~ 3

Author(s):

Fei Xu ◽

Ruitang Cheng ◽

Sunhan Miao ◽

Yuwei Zhu ◽

Ze Sun ◽

...

Keyword(s):

Immune Response ◽

Toxoplasma Gondii ◽

Liver Fibrosis ◽

Schistosoma Japonicum ◽

Hepatic Fibrosis ◽

Intestinal Flora ◽

Therapeutic Interventions ◽

Th2 Response ◽

Th2 Immune Response ◽

Prior Infection

Schistosomiasis is an immunopathogenic disease in which a T helper (Th) cell type 2-like response plays vital roles. Hepatic fibrosis is its main pathologic manifestations, which is the leading cause of hepatic cirrhosis. Co-infections of Schistosoma japonicum (Sj) with other pathogens are frequently encountered but are easily ignored in clinical studies, and effective therapeutic interventions are lacking. In this study, we explored the effect of Toxoplasma gondii (Tg) prior infection on Th1/Th2 response, community shifts in gut microbiome (GM), and the pathogenesis of schistosomiasis in murine hosts. Mice were prior infected with Tg before Sj infection. The effects of co-infection on Th1/Th2 response and hepatic fibrosis were analyzed. Furthermore, we investigated this issue by sequencing 16S rRNA from fecal specimens to define the GM profiles during co-infection. Tg prior infection markedly reduced the granuloma size and collagen deposit in livers against Sj infection. Prior infection promoted a shift toward Th1 immune response instead of Th2. Furthermore, Tg infection promoted the expansion of preponderant flora and Clostridiaceae was identified as a feature marker in the GM of the co-infection group. Redundancy analysis (RDA)/canonical correspondence analysis (CCA) results showed that liver fibrosis, Th1/Th2 cytokines were significantly correlated (P < 0.05) with the GM compositions. Tg infection inhibits hepatic fibrosis by downregulating Th2 immune response against Sj infection, and further promotes the GM shifts through “gut–liver axis” in the murine hosts. Our study may provide insights into potential anti-fibrosis strategies in co-infection individuals.

Download Full-text

Pulmonary arterial remodeling induced by a Th2 immune response

Journal of Experimental Medicine ◽

10.1084/jem.20071008 ◽

2008 ◽

Vol 205 (2) ◽

pp. 361-372 ◽

Cited By ~ 163

Author(s):

Eleen Daley ◽

Claire Emson ◽

Christophe Guignabert ◽

Rene de Waal Malefyt ◽

Jennifer Louten ◽

...

Keyword(s):

Immune Response ◽

Smooth Muscle ◽

Companion Animals ◽

Pulmonary Arteries ◽

Soluble Antigen ◽

Arterial Remodeling ◽

Th2 Response ◽

Experimental Proof ◽

Th2 Immune Response ◽

Pulmonary Arterial

Pulmonary arterial remodeling characterized by increased vascular smooth muscle density is a common lesion seen in pulmonary arterial hypertension (PAH), a deadly condition. Clinical correlation studies have suggested an immune pathogenesis of pulmonary arterial remodeling, but experimental proof has been lacking. We show that immunization and prolonged intermittent challenge via the airways with either of two different soluble antigens induced severe muscularization in small- to medium-sized pulmonary arteries. Depletion of CD4+ T cells, antigen-specific T helper type 2 (Th2) response, or the pathogenic Th2 cytokine interleukin 13 significantly ameliorated pulmonary arterial muscularization. The severity of pulmonary arterial muscularization was associated with increased numbers of epithelial cells and macrophages that expressed a smooth muscle cell mitogen, resistin-like molecule α, but surprisingly, there was no correlation with pulmonary hypertension. Our data are the first to provide experimental proof that the adaptive immune response to a soluble antigen is sufficient to cause severe pulmonary arterial muscularization, and support the clinical observations in pediatric patients and in companion animals that muscularization represents one of several injurious events to the pulmonary artery that may collectively contribute to PAH.

Download Full-text

The ATP bioluminescence assay: a new application and optimization for viability testing in the parasitic nematode Haemonchus contortus

Veterinary Research ◽

10.1186/s13567-021-00980-4 ◽

2021 ◽

Vol 52 (1) ◽

Author(s):

Linh Thuy Nguyen ◽

Markéta Zajíčková ◽

Eva Mašátová ◽

Petra Matoušková ◽

Lenka Skálová

Keyword(s):

Haemonchus Contortus ◽

Gastrointestinal Nematode ◽

Economic Losses ◽

Adult Males ◽

Viability Testing ◽

Third Stage ◽

Maximal Sensitivity ◽

Atp Bioluminescence ◽

Bioluminescence Assay ◽

Atp Bioluminescence Assay

AbstractThe parasitic gastrointestinal nematode Haemonchus contortus causes serious economic losses to agriculture due to infection and disease in small ruminant livestock. The development of new therapies requires appropriate viability testing, with methods nowadays relying on larval motility or development using procedures that involve microscopy. None of the existing biochemical methods, however, are performed in adults, the target stage of the anthelmintic compounds. Here we present a new test for the viability of H. contortus adults and exsheathed third-stage larvae which is based on a bioluminescent assay of ATP content normalized to total protein concentration measured using bicinchoninic acid. All the procedure steps were optimized to achieve maximal sensitivity and robustness. This novel method can be used as a complementary assay for the phenotypic screening of new compounds with potential antinematode activity in exsheathed third-stage larvae and in adult males. Additionally, it might be used for the detection of drug-resistant isolates.

Download Full-text