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- Title
Trichinella spiralis Paramyosin Binds to C8 and C9 and Protects the Tissue-Dwelling Nematode from Being Attacked by Host Complement.
- Authors
Zhang, Zhifei; Yang, Jing; Wei, Junfei; Yang, Yaping; Chen, Xiaoqin; Zhao, Xi; Gu, Yuan; Cui, Shijuan; Zhu, Xinping
- Abstract
Background: Paramyosin is a thick myofibrillar protein found exclusively in invertebrates. Evidence suggested that paramyosin from helminths serves not only as a structural protein but also as an immunomodulatory agent. We previously reported that recombinant Trichinella spiralis paramyosin (Ts-Pmy) elicited a partial protective immunity in mice. In this study, the ability of Ts-Pmy to bind host complement components and protect against host complement attack was investigated. Methods and Findings: In this study, the transcriptional and protein expression levels of Ts-Pmy were determined in T. spiralis newborn larva (NBL), muscle larva (ML) and adult worm developmental stages by RT-PCR and western blot analysis. Expression of Ts-Pmy at the outer membrane was observed in NBL and adult worms using immunogold electron microscopy and immunofluorescence staining. Functional analysis revealed that recombinant Ts-Pmy(rTs-Pmy) strongly bound to complement components C8 and C9 and inhibited the polymerization of C9 during the formation of the membrane attack complex (MAC). rTs-Pmy also inhibited the lysis of rabbit erythrocytes (ER) elicited by an alternative pathway-activated complement from guinea pig serum. Inhibition of native Ts-Pmy on the surface of NBL with a specific antiserum reduced larvae viability when under the attack of complement in vitro. In vivo passive transfer of anti-Ts-Pmy antiserum and complement-treated larvae into mice also significantly reduced the number of larvae that developed to ML. Conclusion: These studies suggest that the outer membrane form of T. spiralis paramyosin plays an important role in the evasion of the host complement attack. Author Summary: Trichinellosis is a serious food borne parasitic disease caused by the consumption of meat contaminated with the infective larvae of Trichinella spiralis. The ability of the tissue-dwelling parasite to evade the host complement attack is essential for its survival and for establishing infection in the host. This study describes the expression of paramyosin, a muscular protein in invertebrates, on the surface of Trichinella spiralis and its role in the defense against the host complement attack as a survival strategy. Using a specific antiserum, expression of Trichinella spiralis paramyosin was detected on the outer membrane of the adult worms and newborn larvae. Functional analysis revealed that recombinant Trichinella spiralis paramyosin protein strongly bound human complement components C8 and C9 and inhibited the formation of the complement membrane attack complex. Neutralization with a specific antiserum greatly impaired the protective effect of paramyosin on the viability and infectivity of Trichinella spiralis newborn larva when under attack by complement. These studies suggest that the outer membrane form of Trichinella spiralis paramyosin plays an important role in the evasion of the host complement attack and is therefore a good target for vaccine and pharmaceutical development.
- Subjects
TRICHINELLA spiralis; COMPLEMENT (Immunology); WESTERN immunoblotting; CYTOSKELETAL proteins; PARASITIC diseases
- Publication
PLoS Neglected Tropical Diseases, 2011, Vol 5, Issue 7, p1
- ISSN
1935-2727
- Publication type
Article
- DOI
10.1371/journal.pntd.0001225