Prediction of the secondary structure of SjLLPi1.

BackgroundSchistosomiasis is an important neglected tropical disease necessitating focus. Cercarial proteases are essential for schistosome invasion. Leishmanolysin has been identified as the most predominant protease in Schistosoma japonicum (S. japonicum) cercariae, but the role and mechanism of leishmanolysin in host skin invasion by S. japonicum cercariae remain unclear.Methodology/principal findingsOur bioinformatic analysis revealed the classification of S. japonicum leishmanolysin within the M8 matrix metalloprotease family. We then expressed recombinant S. japonicum leishmanolysin-like peptidase isoform 1 (SjLLPi1) and verified its hydrolytic enzyme activity. Western blotting analysis confirmed high level of SjLLPi1 protein in S. japonicum cercariae. Immunofluorescence staining revealed SjLLPi1 is predominantly present in the acetabular glands and their ducts in the cercarial head. Infection of mice with anti-SjLLPi1 monoclonal antibody treated S. japonicum cercariae significantly reduced worm and egg burden in mice 42 days post-infection. Infection of mice with anti-SjLLPi1 monoclonal antibody treated S. japonicum cercariae also significantly reduced parasite number in mice 7 days post-infection. In addition, treatment of mouse macrophages with SjLLPi1 prompted notable macrophage activation and substantial parasiticidal NO release. Finally, mice infected with anti-SjLLPi1 monoclonal antibody treated cercariae demonstrated a marked reduction in skin-invading parasite numbers as early as 30 min post-infection.Conclusions/significanceOur study indicates that SjLLPi1 aids S. japonicum cercariae penetration into the definitive host by hydrolyzing skin components, thereby facilitating parasite migration and transition to adult worms within the host. These results may provide valuable guidance for vaccine development and control strategy formulation against schistosome infection.