Alpha-Gal Syndrome: Involvement of Amblyomma americanum α-D-Galactosidase and β-1,4 Galactosyltransferase Enzymes in α-Gal Metabolism

• Published in: Frontiers in cellular and infection microbiology 2021-12, Vol.11, p.775371-775371
• Main Authors: Sharma, Surendra Raj, Crispell, Gary, Mohamed, Ahmed, Cox, Cameron, Lange, Joshua, Choudhary, Shailesh, Commins, Scott P, Karim, Shahid
• Format: Article
• Language: English
• Subjects: alpha-D-galactosidase; alpha-gal; alpha-gal syndrome; alpha-Galactosidase - genetics; Amblyomma; Animals; beta-1; Cellular and Infection Microbiology; Food Hypersensitivity; Galactosidases; Galactosyltransferases - genetics; Humans; Immunoglobulin E; red meat allergy; tick
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2021.775371

Alpha-Gal Syndrome (AGS) is an IgE-mediated delayed-type hypersensitivity reaction to the oligosaccharide galactose-α-1, 3-galactose (α-gal) injected into humans from the lone-star tick ( ) bite. Indeed, α-gal is discovered in salivary glands of lone-star tick; however, the tick's specific intrinsic factors involved in endogenous α-gal production and presentation to host during hematophagy are poorly understood. This study aimed to investigate the functional role of two tick enzymes, α-D-galactosidase (ADGal) and β-1,4 galactosyltransferases (β-1,4GalT), in endogenous α-gal production, carbohydrate metabolism, and N-glycan profile in lone-star tick. The ADGal enzyme cleaves terminal α-galactose moieties from glycoproteins and glycolipids, whereas β-1,4GalT transfers α-galactose to a β1,4 terminal linkage acceptor sugars-GlcNAc, Glc, and Xyl-in various processes of glycoconjugate synthesis. An RNA interference approach was utilized to silence ADGal and β-1,4GalT in to examine their function in α-gal metabolism in tick and AGS onset. Silencing of ADGal led to the significant downregulation of genes involved in galactose metabolism and transport in . Immunoblot and N-glycan analysis of the salivary glands showed a significant reduction in α-gal levels in silenced tissues. However, there was no significant difference in the level of α-gal in β-1,4GalT-silenced tick salivary glands. A basophil-activation test showed a decrease in the frequency of activated basophil by ADGal-silenced salivary glands. These results provide an insight into the roles of ADGal and β-1,4GalT in α-gal production and presentation in ticks and the probable involvement in the onset of AGS.