AUTHOR=Shao Shuai , Hao Chunyue , Zhan Bin , Zhuang Qinghui , Zhao Limei , Chen Yi , Huang Jingjing , Zhu Xinping 

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

JOURNAL=Frontiers in Immunology

VOLUME=11

YEAR=2020

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2020.572326

DOI=10.3389/fimmu.2020.572326

ISSN=1664-3224

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