Glycolipidomics of Liver Flukes and Host Tissues during Fascioliasis: Insights from Mass Spectrometry Imaging

Fascioliasis, a zoonotic disease caused by liver flukes of the genus <i>Fasciola</i>, poses significant health threats to both humans and livestock. While some infections remain asymptomatic, others can lead to fatal outcomes, particularly during the acute phase characterized by the migration of immature parasites causing severe liver damage. Through the combination of data acquired via high-spatial-resolution atmospheric-pressure scanning microprobe matrix-assisted laser desorption/ionization mass spectrometry imaging (AP-SMALDI MSI) and nanohydrophilic interaction chromatography tandem mass spectrometry, we investigated glycosphingolipids (GSLs) in both adult and immature parasite stages as well as the host liver and bile duct to unravel the intricacies of the host-pathogen interplay and associated pathology. Several GSLs showed characteristic distribution patterns within the parasite depending on the fatty acid composition of their ceramides, notably including GSLs carrying very long-chain fatty acids. Additionally, GSL compositions within the tegument of immature versus adult parasites varied, suggestive of tissue remodeling upon maturation. AP-SMALDI MSI further enabled the identification of GSLs potentially involved in <i>in vivo</i> interactions between the host and immature parasites. Moreover, our experiments unveiled alterations in other lipid classes during <i>Fasciola</i> infection, providing a broader understanding of lipidomic changes associated with the disease. Collectively, our findings contribute to a deeper comprehension of the molecular intricacies underlying fascioliasis, with a specific focus on GSLs.