AUTHOR=Zhao Limei , Shao Shuai , Chen Yi , Sun Ximeng , Sun Ran , Huang Jingjing , Zhan Bin , Zhu Xinping 

TITLE=Trichinella spiralis Calreticulin Binds Human Complement C1q As an Immune Evasion Strategy

JOURNAL=Frontiers in Immunology

VOLUME=8

YEAR=2017

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.00636

DOI=10.3389/fimmu.2017.00636

ISSN=1664-3224

ABSTRACT=<p>As a multicellular parasitic nematode, <italic>Trichinella spiralis</italic> regulates host immune responses by producing a variety of immunomodulatory molecules to escape from host immune attack, but the mechanisms underlying the immune evasion are not well understood. Here, we identified that <italic>T. spiralis</italic> calreticulin (<italic>Ts</italic>-CRT), a Ca<sup>2+</sup>-binding protein, facilitated <italic>T. spiralis</italic> immune evasion by interacting with the first component of human classical complement pathway, C1q. In the present study, <italic>Ts</italic>-CRT was found to be expressed on the surface of different developmental stages of <italic>T. spiralis</italic> as well as in the secreted products of adult and muscle larval worms. Functional analysis identified that <italic>Ts</italic>-CRT was able to bind to human C1q, resulting in the inhibition of C1q-initiated complement classical activation pathway reflected by reduced C4/C3 generation and C1q-dependent lysis of antibody-sensitized sheep erythrocytes. Moreover, recombinant <italic>Ts</italic>-CRT (r<italic>Ts</italic>-CRT) binding to C1q suppressed C1q-induced THP-1-derived macrophages chemotaxis and reduced monocyte–macrophages release of reactive oxygen intermediates (ROIs). Blocking <italic>Ts</italic>-CRT on the surface of newborn larvae (NBL) of <italic>T. spiralis</italic> with anti-<italic>Ts</italic>-CRT antibody increased the C1q-mediated adherence of monocyte–macrophages to larvae and impaired larval infectivity. All of these results suggest that <italic>T. spiralis</italic>-expressed <italic>Ts</italic>-CRT plays crucial roles in <italic>T. spiralis</italic> immune evasion and survival in host mostly by directly binding to host complement C1q, which not only reduces C1q-mediated activation of classical complement pathway but also inhibits the C1q-induced non-complement activation of macrophages.</p>