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 <i>Echinococcus multilocularis</i> larvae. To survive within the host, <i>E. multilocularis</i> has developed a complex immune evasion mechanism including the inhibition of complement activation. This study focused on a calreticulin secreted by <i>E. multilocularis</i> (<i>Em</i>CRT) 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 <i>Em</i>CRT 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 <i>Em</i>CRT. 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 <i>Em</i>CRT plays an important role in the immune evasion of <i>E. multilocularis</i> alveolar larvae against host complement attack as a survival strategy within human tissue. This study supports the approach of using <i>Em</i>CRT as a good candidate for vaccine and drug development against <i>E. multilocularis</i> infection.