How does galectin-11 mediate gastrointestinal nematode resistance in sheep?

Abstract

Due to widespread anthelmintic resistance, alternative methods to control gastrointestinal nematodes (GIN) are required. Breeding GIN resistant sheep is a sustainable alternative form of control. As the immune response is responsible for resistance, understanding mechanisms mediating resistance would aid such selection. Galectin-11 is a protein secreted from host epithelial cells into the mucus during GIN infections and its function is unknown. Previous literature has supported the role for galectin-11 in resistance against GIN, 'Haemonchus contortus' ('H. contortus') (Robinson et al., 2011). Therefore the overall aim of this project was to investigate the interaction between galectin-11 and 'H. contortus' in order to define a function. Firstly, immunofluorescent studies were employed to determine if galectin-11 bound to 'H. contortus'. Results showed that recombinant galectin-11 binds to the surface of 'H. contortus' L4 but not L3. Additionally, native galectin-11 was found to bind the surface of 'H. contortus' adults which were directly collected from an infected animal. To explore the possible effect of galectin-11 binding to 'H. contortus' L4, an in vitro assay which monitors the exsheathment of L3 to L4 was developed. Interestingly, recombinant galectin-11 was found to significantly inhibit the exsheathment of L3 to L4 by approximately 50% compared to control treatments (29.4±7.8 cf 73±3.7, p=0.001, respectively). Preliminary research is also indicating a detrimental effect of recombinant galectin-11 on L4 growth in vitro. In summary, we have shown that galectin-11 binds to the surface of L4 and adult H. contortus and can interfere with the development of L3 to L4 in vitro. Future studies aim to identify the native ligand of galectin-11. It is anticipated that further understanding of the interaction between galectin-11 and 'H. contortus' will be important to comprehend the mechanisms associated with GIN immunity and support future investigation of galectin-11 as a potential genetic marker of GIN resistance.