Recombinant Trichinella pseudospiralis Serine Protease Inhibitors Alter Macrophage Polarization In Vitro

Abstract

During parasite infection, serine protease inhibitors secreted by parasites play important roles in suppressing host defenses. However, the mechanism of immune regulation is unclear. In this study, a serpin gene from <i>Trichinella pseudospiralis</i>, named <i>Tp</i>-Serpin, was cloned and expressed, in order to reveal its role in the regulation of the host immune response in <i>T. pseudospiralis</i> infection. The results showed that <i>Tp</i>-Serpin encodes a 43 kDa protein that was recognized by serum from <i>T. pseudospiralis</i> infected mice at 60 days post-infection (dpi). <i>Tp</i>-Serpin was found to be expressed at all developmental stages of <i>T. pseudospiralis</i>. Inhibitory activity analysis showed that recombinant <i>Tp</i>-Serpin (r<i>Tp</i>-Serpin) effectively inhibited the hydrolytic activity of porcine pancreatic elastase (elastase P), human neutrophil elastase (elastase H), and mouse mast cell protease-1, but showed little inhibitory for human neutrophil cathepsin G (cathepsin G). Furthermore, r<i>Tp</i>-Serpin induced polarization of macrophages toward the alternatively activated phenotype (M2) alone by activation of the signal transducer and activator of transcription 3 signaling pathway, and inhibited lipopolysaccharide-induced classically activation (M1) <i>in vitro</i>. These data preliminarily demonstrate that <i>Tp</i>-Serpin may play an important role in the immunoregulation of <i>T. pseudospiralis</i> infection by activating the M2-polarized signaling pathway.