Abstract
The physical barrier is composed of epithelial cells which are joined together through intercellular connections. It serves to prevent pathogenic microorganisms from departing the intestinal lumen to invade the host. The excretory secretory (ES) products of Trichinella spiralis are critical for invasion. However, whether ES products of T. spiralis can act on the intestinal barrier is still unknown. In this study, the role of ES products of T. spiralis muscle larvae (Ts-ML-ES) in host invasion was studied by establishing an in vitro cell monolayers model. Barrier integrity analysis by a transmembrane resistance test and a paracellular permeability assay revealed that the Ts-ML-ES was able to destroy barrier function. It occurred via a reduction in the expression of tight junction (TJ) proteins, which was induced by serine protease. Furthermore, Western bolt analysis indicated that Ts-ML-ES reduced the expression of TJ proteins via the MAPK signaling pathway. Based on these data, we conclude that serine protease are likely the main factors from Ts-ML-ES that affect host intestinal barrier integrity by reducing the expression of TJs via the P38-MAPK signaling pathway. Serine protease in Ts-ML-ES might be a key invasion factor in T. spiralis.
Highlights
For ingested pathogens such as bacteria and parasites, surviving encounters with the host stomach acid, proteases, mucus, and antimicrobial peptides (AMPs), they will encounter the intestinal epithelial cells (IECs) and the other intestinal barrier (Wood, 1993)
When Caco-2 cells were treated with Ts-ML-excretory secretory (ES) at 0–50 μg/ ml for 24 or 48 h, significant reduction of viability was observed only in the 50 μg/ml × 48 h treatment group, but not in any of other groups (Figure 1). 25 μg/ml Ts-ML-ES were used in subsequent experiments
The FITC-dextran across the membranes increased by 300 and 500% in groups treated with Ts-ML-ES, a TNF-α, respectively (Figure 2B)
Summary
For ingested pathogens such as bacteria and parasites, surviving encounters with the host stomach acid, proteases, mucus, and antimicrobial peptides (AMPs), they will encounter the intestinal epithelial cells (IECs) and the other intestinal barrier (Wood, 1993). The intestinal barrier defines the morphological and functional units responsible for protecting the intestinal mucosa, including intestinal flora, IECs and complex cytokine networks, AMPs, and many regulatory molecules (Meng et al, 2017). Epithelial cells and their connections constitute the physical barrier of the intestine, which serves a crucial function in preventing the invasion of pathogenic microorganisms. Several transmembrane proteins help to create TJs: TJ-related MARVEL (MAL and related proteins for vesicle trafficking and membrane) proteins (TAMP) including Occludin, tricellulin (limited to three-cell junction) and MarvelD3; claudins, a 27-member family, a single-span transmembrane protein that interacts in the same direction as the extracellular domain of claudins on adjacent cells; and, a single transmembrane immunoglobulin-like attachment adhesion molecule (JAMs; Odenwald and Turner, 2017). Disruption of TJs resulted in intestinal epithelial barrier dysfunction, and increased microbial invasion of tissues (Betanzos et al, 2013)
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