Research Article: Trichinella spiralis Paramyosin Binds Human Complement C1q and Inhibits Classical Complement Activation

Date Published: December 31, 2015

Publisher: Public Library of Science

Author(s): Ran Sun, Xi Zhao, Zixia Wang, Jing Yang, Limei Zhao, Bin Zhan, Xinping Zhu, Elizabeth Angelica Leme Martins.

Abstract: BackgroundTrichinella spiralis expresses paramyosin (Ts-Pmy) as a defense mechanism. Ts-Pmy is a functional protein with binding activity to human complement C8 and C9 and thus plays a role in evading the attack of the host’s immune system. In the present study, the binding activity of Ts-Pmy to human complement C1q and its ability to inhibit classical complement activation were investigated.Methods and FindingsThe binding of recombinant and natural Ts-Pmy to human C1q were determined by ELISA, Far Western blotting and immunoprecipitation, respectively. Binding of recombinant Ts-Pmy (rTs-Pmy) to C1q inhibited C1q binding to IgM and consequently inhibited C3 deposition. The lysis of antibody-sensitized erythrocytes (EAs) elicited by the classical complement pathway was also inhibited in the presence of rTs-Pmy. In addition to inhibiting classical complement activation, rTs-Pmy also suppressed C1q binding to THP-1-derived macrophages, thereby reducing C1q-induced macrophages migration.ConclusionOur results suggest that T. spiralis paramyosin plays an important role in immune evasion by interfering with complement activation through binding to C1q in addition to C8 and C9.

Partial Text: Trichinellosis is a serious zoonotic disease caused by the ingestion of undercooked meat contaminated with the larvae of Trichinella spiralis. Heavy infection can result in death [1]. Recently, trichinellosis has been regarded as an emerging or re-emerging disease in some countries due to improvements in people’s living standards and changes in eating habits [2,3]. To establish parasitism in the host, T. spiralis has evolved sophisticated mechanisms to avoid immune attack from the host. Elucidating the mechanisms developed by the parasite to survive in the host would facilitate the development of strategies to interrupt parasitism and prevent infection.

Complement activation is regarded as the initial guardian for pathogen elimination. Due to the fundamental role of the complement system in immune defense, evading complement system attack is a crucial step for the survival of pathogens. Many studies have reported immune evasion strategies developed by pathogens targeting complement. For example, the Staphylococcus complement inhibitor (SCIN) inhibited complement C3 convertases, and Pseudomonas elastase (PaE) inhibited C3 in a proteolytic degradation-dependent manner [31]. Pathogens including bacteria, viruses and parasites seem to share similar strategies to escape the immune attack by complement. However, the mechanisms underlying the evasion from complement attack developed by T. spiralis were not well investigated.



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