C57BL/6 α-1,3-Galactosyltransferase Knockout Mouse as an Animal Model for Experimental Chagas Disease

Ayala, Edward Valencia; Cunha, Gisele Macedo Rodrigues da; Azevedo, Maíra Araújo; Calderón, Maritza; Jimenez, Juan A.; Venuto, Ana Paula; Gazzinelli, Ricardo T.; LaValle, Raúl Jesus Ynocente; Riva, Angela Giovana Vidal; Hincapie, Robert; Finn, M. G.; Marques, Alexandre F.

doi:10.1021/acsinfecdis.0c00061

Cited by 8 publications

(8 citation statements)

References 85 publications

(127 reference statements)

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Section: Treatment/management Methodsmentioning

confidence: 99%

“…122 The humanized murine model of this strain for studying AGS (GTKO, AGKO or α1,3-GalT-KO), has been used for the study of tick-induced IgE response-model for α-Gal reactions, 123,124 but also for testing other immunological approaches as tick-borne allergies and Chagas disease investigation. 125,126 Using these animal models, further research is needed to investigate AGS risk factors and epidemiology in order to propose an accurate treatment strategy for each patient.…”

Section: Current Research Methodsmentioning

confidence: 99%

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Current and Future Strategies for the Diagnosis and Treatment of the Alpha-Gal Syndrome (AGS)

Vaz-Rodrigues¹,

Mazuecos²,

Fuente³

2022

JAA

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The α-Gal syndrome (AGS) is a pathognomonic immunoglobulin E (IgE)-mediated delayed anaphylaxis in foods containing the oligosaccharide galactose-α-1,3-galactose (α-Gal) such as mammalian meat or dairy products. Clinical presentation of AGS can also comprise immediate hypersensitivity due to anticancer therapy, gelatin-containing vaccines or mammalian serum-based antivenom. The IgE initial sensitization is caused by hard-bodied tick bites and symptomatic individuals typically develop delayed pruritus, urticaria, angioedema, anaphylaxis, malaise or gut-related symptoms. Due to inapparent presentation, delayed reactions and a wide variety of patients´ clinical history, the AGS diagnosis and treatment remain challenging. This review covers not only current diagnostic methods used for AGS such as the skin prick test (SPT), the oral food challenge (OFC), anti-α-Gal IgE levels measurement and the basophil activation test (BAT), but also potentially relevant next-generation diagnostic tools like the mast cell activation test (MAT), the histamine-release (HR) assay, omics technologies and model-based reasoning (MBR). Moreover, it focuses on the therapeutical medical and non-medical methods available and current research methods that are being applied in order to elucidate the molecular, physiological and immune mechanisms underlying this allergic disorder. Lastly, future treatment and preventive tools are also discussed, being of utmost importance for the identification of tick salivary molecules, with or without α-Gal modifications, that trigger IgE sensitivity as they could be the key for further vaccine development. Bearing in mind climate change, the tick-host paradigm will shift towards an increasing number of AGS cases in new regions worldwide, which will pose new challenges for clinicians in the future.

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Section: Treatment/management Methodsmentioning

confidence: 99%

Section: Current Research Methodsmentioning

confidence: 99%

Current and Future Strategies for the Diagnosis and Treatment of the Alpha-Gal Syndrome (AGS)

Vaz-Rodrigues¹,

Mazuecos²,

Fuente³

2022

JAA

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“…Old-World primates [22,23,75] of producing high titers of anti-α-Gal antibodies [76]. Having earlier found that the virus-like particle bearing a high density of α-Gal is an effective experimental vaccine candidate against Leishmania spp., [28] we describe here the application of this particle to T. cruzi.…”

Section: Plos Neglected Tropical Diseasesmentioning

confidence: 99%

α-Gal immunization positively impacts Trypanosoma cruzi colonization of heart tissue in a mouse model

et al. 2021

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Chagas disease, caused by the parasite Trypanosoma cruzi, is considered endemic in more than 20 countries but lacks both an approved vaccine and limited treatment for its chronic stage. Chronic infection is most harmful to human health because of long-term parasitic infection of the heart. Here we show that immunization with a virus-like particle vaccine displaying a high density of the immunogenic α-Gal trisaccharide (Qβ-αGal) induced several beneficial effects concerning acute and chronic T. cruzi infection in α1,3-galactosyltransferase knockout mice. Approximately 60% of these animals were protected from initial infection with high parasite loads. Vaccinated animals also produced high anti-αGal IgG antibody titers, improved IFN-γ and IL-12 cytokine production, and controlled parasitemia in the acute phase at 8 days post-infection (dpi) for the Y strain and 22 dpi for the Colombian strain. In the chronic stage of infection (36 and 190 dpi, respectively), all of the vaccinated group survived, showing significantly decreased heart inflammation and clearance of amastigote nests from the heart tissue.

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“…It is not totally understood why this mutation could prevail, but it must have provided an evolutionary survival advantage. Indeed, anti-alpha-gal IgG antibodies significantly improve the immune defense against pathogens expressing the epitope like Plasmodium species and Trypanosoma cruzi ( 47 – 49 ). Accordingly, human anti-alpha-gal IgG were also shown to bind to a number of Gram-positive and Gram-negative bacterial pathogens ( 41 ).…”

Section: Carbohydrates As Important Epitopes In Type I Allergymentioning

confidence: 99%

The History of Carbohydrates in Type I Allergy

et al. 2020

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Although first described decades ago, the relevance of carbohydrate specific antibodies as mediators of type I allergy had not been recognized until recently. Previously, allergen specific IgE antibodies binding to carbohydrate epitopes were considered to demonstrate a clinically irrelevant cross-reactivity. However, this changed following the discovery of type I allergies specifically mediated by oligosaccharide structures. Especially the emerging understanding of red meat allergy characterized by IgE directed to the oligosaccharide alpha-gal showed that carbohydrate-mediated reactions can result in life threatening systemic anaphylaxis which in contrast to former assumptions proves a high clinical relevance of some carbohydrate allergens. Within the scope of this review article, we illustrate the historical development of carbohydrate-allergen-research, reaching from only diagnostically relevant crossreactive-carbohydrate-determinants to clinically important antigens mediating type I allergy. Focusing on clinical and immunological features of the alpha-gal syndrome, we highlight the discovery of oligosaccharides as potentially highly immunogenic antigens and mediators of type I allergy, report what is known about the route of sensitization and the immunological mechanisms involved in sensitization and elicitation phase of allergic responses as well as currently available diagnostic and therapeutic tools. Finally, we briefly report on carbohydrates being involved in type I allergies different from alpha-gal.

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C57BL/6 α-1,3-Galactosyltransferase Knockout Mouse as an Animal Model for Experimental Chagas Disease

Cited by 8 publications

References 85 publications

Current and Future Strategies for the Diagnosis and Treatment of the Alpha-Gal Syndrome (AGS)

Current and Future Strategies for the Diagnosis and Treatment of the Alpha-Gal Syndrome (AGS)

α-Gal immunization positively impacts Trypanosoma cruzi colonization of heart tissue in a mouse model

The History of Carbohydrates in Type I Allergy

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