Dataset Information

The alpha-Gal syndrome: new insights into the tick-host conflict and cooperation.

ABSTRACT: This primer focuses on a recently diagnosed tick-borne allergic disease known as the alpha-Gal syndrome (AGS). Tick bites induce in humans high levels of IgE antibodies against the carbohydrate Gal?1-3Gal?1-(3)4GlcNAc-R (?-Gal) present on tick salivary glycoproteins and tissues of non-catarrhine mammals, leading to the AGS in some individuals. This immune response evolved as a conflict and cooperation between ticks and human hosts including their gut microbiota. The conflict is characterized by the AGS that mediate delayed anaphylaxis to red meat consumption and certain drugs such as cetuximab, and immediate anaphylaxis to tick bites. The cooperation is supported by the capacity of anti-?-Gal IgM and IgG antibody response to protect against pathogens with ?-Gal on their surface. Despite the growing diagnosis of AGS in all world continents, many questions remain to be elucidated on the tick proteins and immune mechanisms triggering this syndrome, and the protective response against pathogen infection elicited by anti-?-Gal antibodies. The answer to these questions will provide information for the evaluation of risks, diagnosis and prevention of the AGS, and the possibility of using the carbohydrate ?-Gal to develop vaccines for the control of major infectious diseases.

SUBMITTER: de la Fuente J

PROVIDER: S-EPMC6448316 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The alpha-Gal syndrome: new insights into the tick-host conflict and cooperation.

de la Fuente José J Pacheco Iván I Villar Margarita M Cabezas-Cruz Alejandro A

Parasites & vectors 20190403 1

This primer focuses on a recently diagnosed tick-borne allergic disease known as the alpha-Gal syndrome (AGS). Tick bites induce in humans high levels of IgE antibodies against the carbohydrate Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal) present on tick salivary glycoproteins and tissues of non-catarrhine mammals, leading to the AGS in some individuals. This immune response evolved as a conflict and cooperation between ticks and human hosts including their gut microbiota. The conflict is characterized by ...[more]

PMID: 30944017

Similar Datasets

Project description:IntroductionAlpha-gal syndrome (AGS) is characterized by delayed hypersensitivity to non-primate mammalian meat in people having specific immunoglobulin E (sIgE) to the oligosaccharide galactose-alpha-1,3-galactose. AGS has been linked to tick bites from Amblyomma americanum (Aa) in the U.S. A small animal model of meat allergy is needed to study the mechanism of alpha-gal sensitization, the effector phase leading to delayed allergic responses and potential therapeutics to treat AGS.MethodsEight- to ten-weeks old mice with a targeted inactivation of alpha-1,3-galactosyltransferase (AGKO) were injected intradermally with 50 μg of Aa tick salivary gland extract (TSGE) on days 0, 7, 21, 28, 42, and 49. Total IgE and alpha-gal sIgE were quantitated on Day 56 by enzyme-linked immunosorbent assay. Mice were challenged orally with 400 mg of cooked pork kidney homogenate or pork fat. Reaction severity was assessed by measuring a drop in core body temperature and scoring allergic signs.ResultsCompared to control animals, mice treated with TSGE had 190-fold higher total IgE on Day 56 (0.60 ± 0.12 ng/ml vs. 113.2 ± 24.77 ng/ml; p < 0.001). Alpha-gal sIgE was also produced in AGKO mice following TSGE sensitization (undetected vs. 158.4 ± 72.43 pg/ml). Further, sensitized mice displayed moderate clinical allergic signs along with a drop in core body temperature of ≥2°C as an objective measure of a systemic allergic reaction. Interestingly, female mice had higher total IgE responses to TSGE treatment but male mice had larger declines in mean body temperature.ConclusionTSGE-sensitized AGKO mice generate sIgE to alpha-gal and demonstrate characteristic allergic responses to pork fat and pork kidney. In keeping with the AGS responses documented in humans, mice reacted more rapidly to organ meat than to high fat pork challenge. This mouse model establishes the central role of tick bites in the development of AGS and provides a small animal model to mechanistically study mammalian meat allergy.

Project description:This study provides a multi-omics approach to determine the effect on the transcriptome and proteome gut profiles of zebrafish inoculated with tick saliva followed by mammalian meat consumption. With bioinformatics analysis using the R software, we sought for significant biological and metabolic pathway changes, in order to fill up some of the current knowledge gaps associated with the alpha-Gal syndrome (AGS). In addition, ortholog mapping allowed to obtain highly concordant biological 1:1 human ortholog genes for the detection of gene-disease associations (GDAs) and disease enriched pathways. Further data validation was performed using reverse transcriptase quantitative PCR (RT-qPCR) and Western Blot (WB) analysis on target differentially expressed genes (DEGs) and differentially represented proteins (DRPs), respectively. We found that treatment with tick saliva increased mortality and caused significant higher incidence of hemorrhagic type allergic reactions, changes in behavior and feeding patterns. Transcriptomics analysis showed downregulation of biological and metabolic pathways correlated with anti-Gal IgE and allergic reactions to tick saliva such as blood circulation, cardiac and vascular smooth muscle contraction, behavior and sensory perception. Disease enrichment analysis revealed that downregulated orthologous genes were mostly associated with human disorders affecting the nervous, musculoskeletal, and cardiovascular systems. Proteomics analysis predominantly revealed suppression of biological and metabolic pathways associated with the immune system production of reactive oxygen species (ROS) and cardiac muscle contraction. The underrepresented proteins were mainly linked to nervous and nutritional/metabolic human disorders. Furthermore, 12 DEGs were found to have concomitant protein-level representation. Lastly, the integration of transcriptomics and proteomics layers through multi-omics pathway enrichment revealed inhibition of pathways associated with adrenergic signaling in cardiomyocytes, as well as heart and muscle contraction. This research contributed to the discovery of AGS-related biological pathways, reinforcing disease multisystemic organ involvement and linking α-Gal sensitization with other illnesses. Furthermore, our results shed light on novel bioinformatic strategies for the identification of key genes and proteins that may serve as potential disease biomarkers.

Dataset Information

The alpha-Gal syndrome: new insights into the tick-host conflict and cooperation.

Publications

The alpha-Gal syndrome: new insights into the tick-host conflict and cooperation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets