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Trichinella spiralis Calreticulin S-Domain Binds to Human Complement C1q to Interfere With C1q-Mediated Immune Functions.


ABSTRACT: Helminths develop strategies to escape host immune responses that facilitate their survival in the hostile host immune environment. Trichinella spiralis, a tissue-dwelling nematode, has developed a sophisticated strategy to escape complement attack. Our previous study demonstrated that T. spiralis secretes calreticulin (TsCRT) to inhibit host classical complement activation through binding to C1q; however, the C1q binding site in TsCRT and the specific mechanism involved with complement-related immune evasion remains unknown. Using molecular docking modeling and fragment expression, we determined that TsCRT-S, a 153-aa domain of TsCRT, is responsible for C1q binding. Recombinant TsCRT-S protein expressed in Escherichia coli had the same capacity to bind and inhibit human C1q-induced complement and neutrophil activation, as full-length TsCRT. TsCRT-S inhibited neutrophil reactive oxygen species and elastase release by binding to C1q and reduced neutrophil killing of newborn T. spiralis larvae. Binding of TsCRT-S to C1q also inhibited formation of neutrophil extracellular traps (NETs), which are involved in autoimmune pathologies and have yet to be therapeutically targeted. These findings provide evidence that the TsCRT-S fragment, rather than the full-length TsCRT, is a potential target for vaccine or therapeutic development for trichinellosis, as well as for complement-related autoimmune disease therapies.

SUBMITTER: Shao S 

PROVIDER: S-EPMC7710684 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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<i>Trichinella spiralis</i> Calreticulin S-Domain Binds to Human Complement C1q to Interfere With C1q-Mediated Immune Functions.

Shao Shuai S   Hao Chunyue C   Zhan Bin B   Zhuang Qinghui Q   Zhao Limei L   Chen Yi Y   Huang Jingjing J   Zhu Xinping X  

Frontiers in immunology 20201119


Helminths develop strategies to escape host immune responses that facilitate their survival in the hostile host immune environment. <i>Trichinella spiralis</i>, a tissue-dwelling nematode, has developed a sophisticated strategy to escape complement attack. Our previous study demonstrated that <i>T. spiralis</i> secretes calreticulin (<i>Ts</i>CRT) to inhibit host classical complement activation through binding to C1q; however, the C1q binding site in <i>Ts</i>CRT and the specific mechanism invol  ...[more]

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