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 Trichinella pseudospiralis, named Tp-Serpin, was cloned and expressed, in order to reveal its role in the regulation of the host immune response in T. pseudospiralis infection. The results showed that Tp-Serpin encodes a 43 kDa protein that was recognized by serum from T. pseudospiralis infected mice at 60 days post-infection (dpi). Tp-Serpin was found to be expressed at all developmental stages of T. pseudospiralis. Inhibitory activity analysis showed that recombinant Tp-Serpin (rTp-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, rTp-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) in vitro. These data preliminarily demonstrate that Tp-Serpin may play an important role in the immunoregulation of T. pseudospiralis infection by activating the M2-polarized signaling pathway.
Highlights
Trichinella is an intracellular parasite of skeletal muscle that can infect a wide variety of mammalian species and some carnivorous birds
Based on the structural prediction, Tp-serine protease inhibitors (Serpins) consists of 60.71% α-helices and 39.29% β-sheets, and the solvent-exposed reactive center loop is near the C-terminus (Figures 1A,C)
The results indicated that Tp-Serpin is genetically related to Ts-Serpin, from T. spiralis, and are more closely related to nematode serpins than vertebrate serpins (Figure 1B)
Summary
Trichinella is an intracellular parasite of skeletal muscle that can infect a wide variety of mammalian species and some carnivorous birds. Trichinella, as with other helminths, can ensure its survival by modulating the host immunological response (SofronicMilosavljevic et al, 2015). Induction of host immunosuppression is an important strategy for Trichinella pseudospiralis Serpins Alter Macrophage Polarization pathogens to invade their hosts and is a common characteristic of helminth infections. Trichinella is one of the few parasites with the extremely strong ability to induce host immune suppression (Bruschi, 2002). Several studies have shown that Trichinella infection can alleviate or inhibit various immune-related diseases, including type I diabetes, experimental allergic encephalitis, inflammatory bowel disease, and airway allergic inflammation (Park et al, 2011; Wang et al, 2016)
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