Binding of Trichinella spiralis C-type lectin with syndecan-1 on intestinal epithelial cells mediates larval invasion of intestinal epithelium

• Published in: Veterinary research (Paris) Vol. 54; no. 1; p. 86
• Main Authors: Wang, Zhen, Lu, Qi Qi, Weng, Min Min, Li, Yang Li, Han, Lu Lu, Song, Yan Yan, Shi, Yu Long, Liu, Ruo Dan, Cui, Jing, Wang, Zhong Quan
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 02.10.2023; BioMed Central; BMC
• Subjects: Animals; C-type lectin; Caco-2 Cells; E coli; Epithelial Cells - metabolism; Epithelium; Ethylenediaminetetraacetic acid; Extracellular matrix; Health aspects; Heparan sulfate; Humans; Infections; intestinal epithelium; Intestinal Mucosa - metabolism; invasion; Larva - physiology; Lectins; Ligands; Mice; Mice, Inbred BALB C; Plasmids; Protein binding; Proteins; Sulfates; syndecan-1; Syndecan-1 - genetics; Syndecan-1 - metabolism; T cells; Trichinella spiralis; Trichinella spiralis - physiology; Trichinellosis - parasitology; Trichinellosis - veterinary; China; United States > US; Trichinella spiralis; intestinal epithelium; syndecan-1; invasion; C-type lectin
• ISSN: 1297-9716; 0928-4249; 1297-9716
• DOI: 10.1186/s13567-023-01217-2

C-type lectin (CTL) is a protein that binds to saccharides and plays an important role in parasite adhesion, host cell invasion and immune evasion. Previous studies showed that recombinant T. spiralis C-type lectin (rTsCTL) promotes larval invasion of intestinal epithelium cells (IEC), whereas anti-rTsCTL antibodies inhibits larval invasion. Syndecan-1 (SDC-1) is a member of the heparan sulfate proteoglycan family which is mainly expressed on the surface of IEC and in extracellular matrices where they interact with a plethora of ligands. SDC-1 has a principal role in maintaining cell morphogenesis, establishing cell-cell adhesions, and regulating the gut mucosal barrier. The aim of this study was to investigate whether rTsCTL binds to SDC-1 on IEC, and the binding of rTsCTL with SDC-1 promotes larval invasion and its mechanism. IFA results show that rTsCTL and SDC-1 co-localized on Caco-2 cell membrane. GST pull-down and Co-IP verified the direct interaction between rTsCTL and SDC-1 on Caco-2 cells. qPCR and Western blotting revealed that rTsCTL binding to SDC-1 increased the expression of SDC-1 and claudin-2, and reduced the expression of occludin and claudin-1 in Caco-2 cells incubated with rTsCTL via the STAT3 pathway. β-Xyloside (a syndecan-1 synthesis inhibitor) and Stattic (a STAT3 inhibitor) significantly inhibited rTsCTL binding to syndecan-1 in Caco-2 cells and activation of the STAT3 pathway, abrogated the effects of rTsCTL on the expression of gut tight junctions, and impeded larval invasion. The results demonstrate that binding of rTsCTL to SDC-1 on Caco-2 cells activated the STAT3 pathway, decreased gut tight junction expression, damaged the integrity of the gut epithelial barrier, and mediated T. spiralis invasion of the gut mucosa. TsCTL might be regarded as a candidate vaccine target against T. spiralis invasion and infection.