Echinococcus multilocularis Calreticulin Interferes with C1q-Mediated Complement Activation

As a zoonotic disease caused by Echinococcus multilocularis larvae, alveolar echinococcosis (AE) is one of the most severe forms of parasitic infection. Over a long evolutional process E. multilocularis has developed complex strategies to escape host immune attack and survive within a host. However, the mechanisms underlying immune evasion remain unclear. Here we investigated the binding activity of E. multilocularis calreticulin (EmCRT), a highly conserved Ca²⁺-binding protein, to human complement C1q and its ability to inhibit classical complement activation. ELISA, Far Western blotting and immunoprecipitation results demonstrated that both recombinant and natural EmCRTs bound to human C1q, and the interaction of recombinant EmCRT (rEmCRT) inhibited C1q binding to IgM. Consequently, rEmCRT inhibited classical complement activation manifested as decreasing C4/C3 depositions and antibody-sensitized cell lysis. Moreover, rEmCRT binding to C1q suppressed C1q binding to human mast cell, HMC-1, resulting in reduced C1q-induced mast cell chemotaxis. According to these results, E. multilocularis expresses EmCRT to interfere with C1q-mediated complement activation and C1q-dependent non-complement activation of immune cells, possibly as an immune evasion strategy of the parasite in the host.