Trichinella spiralis galectin disrupts gut epithelial integrity and mediates larval invasion via acting MUC13- ROCK2/MAPK pathway
- 1Department of Parasitology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China
- 2School of Basic Medical Science, Putian University, Key Laboratory of Translational Tumor Medicine in Fujian Province, Putian, China
Abstract
Background: Gut epithelium serves as a critical barrier against Trichinella spiralis larval invasion, parasite-derived galectins are involved in host–parasite interactions, including invasion and immune modulation. This study investigated the role of T. spiralis galectin (Tsgal) in gut epithelial barrier disruption and larval invasion. Methodology/principal findings: Recombinant Tsgal (rTsgal) was expressed in vitro and its interaction with intestinal epithelial cells (IEC) was ascertained using immunofluorescence test (IFT) and confocal microscopy. The rTsgal-specific binding IEC proteins were identified by GST pull-down, mass spectrometry (MS) and Co-immunoprecipitation (Co-IP) assay. Intestinal epithelial integrity damage induced by rTsgal was evaluated by IFT, qPCR and Western blotting analysis. The in vitro larva invasive assay was also conducted. The results showed that rTsgal bound and interacted specifically with MUC13 receptor in Caco-2 cells. rTsgal activated MUC13-ROCK2/MAPK pathway, reduced the expression of gut epithelial tight junctions (TJs; ZO-1, E-cad, Occludin and Claudin-1), increased gut epithelial permeability, disrupted gut epithelial integrity and barrier functions, thereby facilitated larva invasion of Caco-2 monolayers. Moreover, MUC13 receptor inhibitor (Cuc D), MUC13 knockdown of Caco-2 cells, ROCK2 inhibitor (KD025) and p38-MAPK inhibitor (SB203580) suppressed this pathway activation, restored gut epithelial integrity, and impeded larval invasion. Conclusions: Tsgal disrupted gut epithelial integrity and mediated larval invasion through binding to MUC13 receptor and activating ROCK2/MAPK pathway. Tsgal might be a potential target molecule for development of novel drugs and vaccines to block T. spiralis infection. Author summary: Intestinal epithelium is a crucial barrier to defense Trichinella spiralis larva invasion, but the mechanism of larval penetration of gut epithelium remains unclear. Galectin is widely distributed in parasites, and plays a significant act in the invasion process and immunomodulation. Our study aimed to reveal the mechanism of T. spiralis galectin (Tsgal) mediating larval invasion of intestinal epithelium. The results of GST pull-down, mass spectrometry (MS) and Co-IP showed that rTsgal bound and interacted specifically with MUC13 receptor in Caco-2 cells. Trans-epithelial electrical resistance (TEER), gut epithelial paracellular permeability, qPCR and Western blot analysis showed that rTsgal activated MUC13-ROCK2/MAPK pathways, reduced expression levels of gut epithelial tight junctions (TJs; ZO-1, E-cad, Occludin and Claudin-1), increased paracellular permeability and damaged intestinal epithelial integrity, and mediated larva invasion. Moreover, MUC13 receptor inhibitor (Cuc D), MUC13 knockdown of Caco-2 cells, ROCK2 inhibitor (KD025) and p38-MAPK inhibitor (SB203580) inhibited the activation of ROCK2/MAPK pathway, they also abrogated and reduced the rTsgal role on disrupting enteric TJs integrity and barrier function, and impeded larva invasion. Our findings indicated that Tsgal played a critical role in destroying enteric barrier integrity and mediating larva invasion. These insights refined our understanding for T. spiralis larval invasion mechanism and offered a novel potential target for anti-T. spiralis vaccine.
Related
- Serine protease inhibitor from Trichinella spiralis ameliorates diet-induced obesity and adipose tissue inflammation through TIM-3-dependent macrophage reprogramming
- S100A4 enhances the pro-fibrotic effect of macrophage to promote collagen capsule formation of Trichinella spiralis
- SETD3 ACTIN HISTIDINE METHYLTRANSFERASE REGULATES INTESTINAL EPITHELIAL BARRIER INTEGRITY AND MUCOSAL INFLAMMATION
- Exome analysis of Indian ulcerative colitis reveals novel genes affecting epithelial integrity, DNA repair, trafficking, and immune signalling.
- Assessment of epithelial barrier integrity in cellular monolayer models using low cost, clinically approved fluorescent contrast agents
BibTeX
@article{zhang2026trichinella,
title = {{Trichinella spiralis galectin disrupts gut epithelial integrity and mediates larval invasion via acting MUC13- ROCK2/MAPK pathway}},
author = {Ru Zhang and Yao Zhang and Xin Zhuo Zhang and Pei Kun Cong and Jin Yi Wu and Shao Rong Long and Ruo Dan Liu and Jia Xu and Jing Cui and Zhong Quan Wang},
journal = {PLOS Neglected Tropical Diseases},
year = {2026},
month = sep,
doi = {10.1371/journal.pntd.0014684},
url = {https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014684},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Trichinella spiralis galectin disrupts gut epithelial integrity and mediates larval invasion via acting MUC13- ROCK2/MAPK pathway
AU - Ru Zhang
AU - Yao Zhang
AU - Xin Zhuo Zhang
AU - Pei Kun Cong
AU - Jin Yi Wu
AU - Shao Rong Long
AU - Ruo Dan Liu
AU - Jia Xu
AU - Jing Cui
AU - Zhong Quan Wang
PY - 2026
DA - 2026/09/21
JO - PLOS Neglected Tropical Diseases
DO - 10.1371/journal.pntd.0014684
UR - https://journals.plos.org/plosntds/article?id=10.1371/journal.pntd.0014684
AB - Background: Gut epithelium serves as a critical barrier against Trichinella spiralis larval invasion, parasite-derived galectins are involved in host–parasite interactions, including invasion and immune modulation. This study investigated the role of T. spiralis galectin (Tsgal) in gut epithelial barrier disruption and larval invasion. Methodology/principal findings: Recombinant Tsgal (rTsgal) was expressed in vitro and its interaction with intestinal epithelial cells (IEC) was ascertained using immunofluorescence test (IFT) and confocal microscopy. The rTsgal-specific binding IEC proteins were identified by GST pull-down, mass spectrometry (MS) and Co-immunoprecipitation (Co-IP) assay. Intestinal epithelial integrity damage induced by rTsgal was evaluated by IFT, qPCR and Western blotting analysis. The in vitro larva invasive assay was also conducted. The results showed that rTsgal bound and interacted specifically with MUC13 receptor in Caco-2 cells. rTsgal activated MUC13-ROCK2/MAPK pathway, reduced the expression of gut epithelial tight junctions (TJs; ZO-1, E-cad, Occludin and Claudin-1), increased gut epithelial permeability, disrupted gut epithelial integrity and barrier functions, thereby facilitated larva invasion of Caco-2 monolayers. Moreover, MUC13 receptor inhibitor (Cuc D), MUC13 knockdown of Caco-2 cells, ROCK2 inhibitor (KD025) and p38-MAPK inhibitor (SB203580) suppressed this pathway activation, restored gut epithelial integrity, and impeded larval invasion. Conclusions: Tsgal disrupted gut epithelial integrity and mediated larval invasion through binding to MUC13 receptor and activating ROCK2/MAPK pathway. Tsgal might be a potential target molecule for development of novel drugs and vaccines to block T. spiralis infection. Author summary: Intestinal epithelium is a crucial barrier to defense Trichinella spiralis larva invasion, but the mechanism of larval penetration of gut epithelium remains unclear. Galectin is widely distributed in parasites, and plays a significant act in the invasion process and immunomodulation. Our study aimed to reveal the mechanism of T. spiralis galectin (Tsgal) mediating larval invasion of intestinal epithelium. The results of GST pull-down, mass spectrometry (MS) and Co-IP showed that rTsgal bound and interacted specifically with MUC13 receptor in Caco-2 cells. Trans-epithelial electrical resistance (TEER), gut epithelial paracellular permeability, qPCR and Western blot analysis showed that rTsgal activated MUC13-ROCK2/MAPK pathways, reduced expression levels of gut epithelial tight junctions (TJs; ZO-1, E-cad, Occludin and Claudin-1), increased paracellular permeability and damaged intestinal epithelial integrity, and mediated larva invasion. Moreover, MUC13 receptor inhibitor (Cuc D), MUC13 knockdown of Caco-2 cells, ROCK2 inhibitor (KD025) and p38-MAPK inhibitor (SB203580) inhibited the activation of ROCK2/MAPK pathway, they also abrogated and reduced the rTsgal role on disrupting enteric TJs integrity and barrier function, and impeded larva invasion. Our findings indicated that Tsgal played a critical role in destroying enteric barrier integrity and mediating larva invasion. These insights refined our understanding for T. spiralis larval invasion mechanism and offered a novel potential target for anti-T. spiralis vaccine.
SN - 1935-2735
ER -