Characterization of an Interaction between S. mansoni surface protein NPP5 and human immune receptor LAIR-1

Schistosomiasis is an infectious tropical disease that is endemic to Africa, Asia, South America and some parts of Mediterranean Europe. This neglected disease affects over 200 million worldwide, mostly in developing countries, and is often chronic. The Schistosoma worms and larvae can regulate the immune system of their human host, allowing them to remain in the body unaffected. Research into this immunomodulation is at an early stage, and in this work, we aim to characterise an interaction between an S. mansoni protein NPP5 and a human immune receptor LAIR-1. SmNPP5 is an ectoenzyme present on the tegument of the worms and larvae. hLAIR-1 is a human receptor with immunomodulatory functions known for binding collagen: when activated via ligand binding, it will suppress the immune function of the cell it is expressed on. We used recombinant forms of both proteins and determined that the hLAIR-1 binding SmNPP5 through its Ig domain, specifically residues R59 and R65. We have also found that collagen I, the natural hLAIR-1 ligand, competes with SmNPP5 for binding to hLAIR-1. Next, we determined that SmNPP5 is likely a dimer and predicted that it homodimerizes via the residue C410.Finally, we found that the secreted paralog of hLAIR1: hLAIR2, can also bind to SmNPP5 and that this interaction can also be disrupted by collagen I.