Dataset Information

Tick Saliva and the Alpha-Gal Syndrome: Finding a Needle in a Haystack.

ABSTRACT: Ticks and tick-borne diseases are significant public health concerns. Bioactive molecules in tick saliva facilitate prolonged blood-feeding and transmission of tick-borne pathogens to the vertebrate host. Alpha-gal syndrome (AGS), a newly reported food allergy, is believed to be induced by saliva proteins decorated with a sugar molecule, the oligosaccharide galactose-⍺-1,3-galactose (α-gal). This syndrome is characterized by an IgE antibody-directed hypersensitivity against α-gal. The α-gal antigen was discovered in the salivary glands and saliva of various tick species including, the Lone Star tick (Amblyomma americanum). The underlying immune mechanisms linking tick bites with α-gal-specific IgE production are poorly understood and are crucial to identify and establish novel treatments for this disease. This article reviews the current understanding of AGS and its involvement with tick species.

SUBMITTER: Sharma SR

PROVIDER: S-EPMC8331069 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Tick Saliva and the Alpha-Gal Syndrome: Finding a Needle in a Haystack.

Sharma Surendra Raj SR Karim Shahid S

Frontiers in cellular and infection microbiology 20210720

Ticks and tick-borne diseases are significant public health concerns. Bioactive molecules in tick saliva facilitate prolonged blood-feeding and transmission of tick-borne pathogens to the vertebrate host. Alpha-gal syndrome (AGS), a newly reported food allergy, is believed to be induced by saliva proteins decorated with a sugar molecule, the oligosaccharide galactose-⍺-1,3-galactose (α-gal). This syndrome is characterized by an IgE antibody-directed hypersensitivity against α-gal. The α-gal anti ...[more]

PMID: 34354960

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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.

Project description:IntroductionAlpha-Gal Syndrome (AGS) is a delayed allergic reaction due to specific IgE antibodies targeting galactose-α-1,3-galactose (α-gal), a carbohydrate found in red meat. This condition has gained significant attention globally due to its increasing prevalence, with more than 450,000 cases estimated just in the United States alone. Previous research has established a connection between AGS and tick bites, which sensitize individuals to α-gal antigens and elevate the levels of specific IgE. However, the precise mechanism by which tick bites influence the host's immune system and contribute to the development of AGS remains poorly understood. This study investigates various factors related to ticks and the host associated with the development of AGS following a tick bite, using mice with a targeted disruption of alpha-1,3-galactosyltransferase (AGKO) as a model organism.MethodsLone-star tick (Amblyomma americanum) and gulf-coast tick (Amblyomma maculatum) nymphs were used to sensitize AGKO mice, followed by pork meat challenge. Tick bite site biopsies from sensitized and non-sensitized mice were subjected to mRNA gene expression analysis to assess the host immune response. Antibody responses in sensitized mice were also determined.ResultsOur results showed a significant increase in the total IgE, IgG1, and α-gal IgG1 antibodies titers in the lone-star tick-sensitized AGKO mice compared to the gulf-coast tick-sensitized mice. Pork challenge in Am. americanum -sensitized mice led to a decline in body temperature after the meat challenge. Gene expression analysis revealed that Am. americanum bites direct mouse immunity toward Th2 and facilitate host sensitization to the α-gal antigen.ConclusionThis study supports the hypothesis that specific tick species may increase the risk of developing α-gal-specific IgE and hypersensitivity reactions or AGS, thereby providing opportunities for future research on the mechanistic role of tick and host-related factors in AGS development.

Dataset Information

Tick Saliva and the Alpha-Gal Syndrome: Finding a Needle in a Haystack.

Publications

Tick Saliva and the Alpha-Gal Syndrome: Finding a Needle in a Haystack.

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