Trichinella spiralis cathepsin L damages the tight junctions of intestinal epithelial cells and mediates larval invasion.
PLoS Negl Trop Dis
; 17(12): e0011816, 2023 Dec.
Article
en En
| MEDLINE
| ID: mdl-38048314
ABSTRACT
BACKGROUND:
Cathepsin L, a lysosomal enzyme, participates in diverse physiological processes. Recombinant Trichinella spiralis cathepsin L domains (rTsCatL2) exhibited natural cysteine protease activity and hydrolyzed host immunoglobulin and extracellular matrix proteins in vitro, but its functions in larval invasion are unknown. The aim of this study was to explore its functions in T. spiralis invasion of the host's intestinal epithelial cells. METHODOLOGY/PRINCIPALFINDINGS:
RNAi significantly suppressed the expression of TsCatL mRNA and protein with TsCatL specific siRNA-302. T. spiralis larval invasion of Caco-2 cells was reduced by 39.87% and 38.36%, respectively, when anti-TsCatL2 serum and siRNA-302 were used. Mice challenged with siRNA-302-treated muscle larvae (ML) exhibited a substantial reduction in intestinal infective larvae, adult worm, and ML burden compared to the PBS group, with reductions of 44.37%, 47.57%, and 57.06%, respectively. The development and fecundity of the females from the mice infected with siRNA-302-treated ML was significantly inhibited. After incubation of rTsCatL2 with Caco-2 cells, immunofluorescence test showed that the rTsCatL2 gradually entered into the cells, altered the localization of cellular tight junction proteins (claudin 1, occludin and zo-1), adhesion junction protein (e-cadherin) and extracellular matrix protein (laminin), and intercellular junctions were lost. Western blot showed a 58.65% reduction in claudin 1 expression in Caco-2 cells treated with rTsCatL2. Co-IP showed that rTsCatL2 interacted with laminin and collagen I but not with claudin 1, e-cadherin, occludin and fibronectin in Caco-2 cells. Moreover, rTsCatL2 disrupted the intestinal epithelial barrier by inducing cellular autophagy.CONCLUSIONS:
rTsCatL2 disrupts the intestinal epithelial barrier and facilitates T. spiralis larval invasion.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
Problema de salud:
3_helminthiasis
/
3_neglected_diseases
Asunto principal:
Triquinelosis
/
Trichinella spiralis
/
Uniones Estrechas
/
Catepsina L
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
PLoS Negl Trop Dis
Asunto de la revista:
MEDICINA TROPICAL
Año:
2023
Tipo del documento:
Article