Marie-Kristin Raulf - Binding of host C-type lectin receptors to Toxocara spp.-derived ligands – relevance of MGL-1 and MCL in toxocarosis

Réalisation : 29 novembre 2021 Mise en ligne : 29 novembre 2021
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Toxocara canis and Toxocara cati are worldwide-distributed zoonotic intestinal helminths with frequent exposure to humans in which they can cause severe disease pathology. Upon infection, initial recognition of pathogens is mediated by pattern recognition receptors (PRRs), of which myeloid C-type lectin receptors (CLRs) recognise carbohydrate structures of bacteria, virus, fungi and parasites. However, there is a gap of knowledge on whether and how myeloid CLRs recognise Toxocara-derived ligands.Therefore, binding of host CLRs to Toxocara spp. was evaluated by the use of a comprehensive CLR-hFc fusion protein library. ELISA-, immunofluorescence microscopy- and immunoblot-based assays revealed a prominent interaction of Toxocara spp. with the macrophage Gal/GalNAc lectin-1 (MGL-1) and unravelled protein fractions containing potential ligands for MGL-1 and the macrophage C-type lectin (MCL). Ligand identification by LC-MS-based protein analysis showed metalloendopeptidase M12A as a candidate for interaction with MGL-1. Microarray data and cell stimulation assays gave first insights into the immunological relevance of Toxocara/CLR interaction with an upregulation of transcriptomic profiles of both MGL-1 and MCL during infection and an importance for MCL in Toxocara-mediated cytokine secretion.In conclusion, MGL-1 and MCL are promising candidates for immune modulation during Toxocara infection as indicated by the specific binding of these host CLRs to Toxocara-derived antigens.<div>


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