Echinococcus multilocularis Calreticulin Inhibits Lectin Pathway of Complement Activation by Directly Binding to Mannose-Binding Lectin.

Alveolar Echinococcosis (AE) is a serious zoonotic disease caused by infection of Echinococcus multilocularis larvae. To survive within the host, E. multilocularis has developed a complex immune evasion mechanism including the inhibition of complement activation. This study focused on a calreticulin secreted by E. multilocularis (EmCRT) and its role in binding ability to human MBL and inhibiting MBL-mannose-mediated lectin pathway of complement activation. Results demonstrated the binding of recombinant EmCRT protein to both external and natural MBL in serum and the subsequent inhibition of MBL-mannose-initiated lectin pathway reflected by the reduced formation of complement intermediate products C3b and C4b. Fragment mapping determined that the MBL binding site was located within the S-domain of EmCRT. Combining with its role in inhibiting C1q-initiated classical complement activation in our previous study, the inhibition of MBL-mannose-initiated lectin pathway identified in this study suggests EmCRT plays an important role in the immune evasion of E. multilocularis alveolar larvae against host complement attack as a survival strategy within human tissue. This study supports the approach of using EmCRT as a good candidate for vaccine and drug development against E. multilocularis infection.