Abstract
Toxocara canis and Toxocara cati, the worldwide occurring intestinal roundworms of canids and felids, represent an important public health threat due to various disease manifestations in humans. Host recognition of pathogens is mediated by pattern recognition receptors (PRRs). Myeloid C-type lectin receptors (CLRs) are PRRs and recognise carbohydrate structures of various pathogens. As Toxocara excretory-secretory products (TES) are predominantly composed of glycoconjugates, they represent suitable targets for CLRs. However, the range of host-derived CLRs recognising Toxocara spp. is still unknown. Using a CLR-hFc fusion protein library, T. canis and T. cati L3 somatic antigens (TSOM) were bound by a variety of CLRs in enzyme-linked immunosorbent assay (ELISA), while their TES products interacted with macrophage galactose-type lectin-1 (MGL-1). Two prominent candidate CLRs, MGL-1 and macrophage C-type lectin (MCL), were selected for further binding studies. Immunofluorescence microscopy revealed binding of MGL-1 to the oral aperture of L3. Immunoblot experiments identified distinct protein fractions representing potential ligands for MGL-1 and MCL. To evaluate how these interactions influence the host immune response, bone marrow-derived dendritic cell (BMDC) assays were performed, showing MCL-dependent T. cati-mediated cytokine production. In conclusion, MGL-1 and MCL are promising candidates for immune modulation during Toxocara infection, deserving further investigation in the future.
Highlights
Toxocara canis and Toxocara cati, the dog and cat roundworm, are worldwide-distributed intestinal helminths with frequent exposure to humans [1]
T. canis and T. cati T. cati L3 somatic antigens (TSOM) were bound by several C-type lectin receptors (CLRs)-hFc fusion proteins such as macrophage inducible C-type lectin (Mincle), Dectin-1, Dectin-2, SIGNR3, Dendritic Cell-Specific Intercellular adhesion molecule-3-Grabbing Non-integrin (DC-SIGN), CLEC12A, CLEC12B, macrophage galactose-type lectin-1 (MGL-1), macrophage C-type lectin (MCL) and Langerin, indicating a potential role of these CLRs in recognition of Toxocara spp. (Figure 1)
The present study shows the binding of various CRLs to Toxocara TSOM, distinct binding to Toxocara excretory-secretory products (TES) antigens, and reveals two promising candidate CLRs for immune modulation during Toxocara infection: macrophage galactose-type lectin (MGL)-1 and MCL
Summary
Toxocara canis and Toxocara cati, the dog and cat roundworm, are worldwide-distributed intestinal helminths with frequent exposure to humans [1]. Humans can act as paratenic hosts by accidental ingestion of embryonated eggs or larvae in tissues of animal paratenic hosts [2]. Since third-stage larvae (L3) are not able to develop further in the paratenic host after somatic migration, they persist in the tissues of, for example, the liver, muscles, eyes or brain. Thereby, they may cause a broad range of clinical symptoms classified into four different forms of toxocarosis—covert toxocarosis as well as the visceral and ocular larva migrans syndrome and neurotoxocarosis (NT), with high relevance for human health [5]. Migrating and persisting L3 can evade the host immune response, persisting for up to a decade within the paratenic host [6]
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