학술논문

Suppression of inflammatory genes expression in the injured host intestinal wall during Mesocestoides vogae tetrathyridium larvae migration.
Document Type
Article
Source
PLoS Neglected Tropical Diseases. 10/13/2020, Vol. 14 Issue 10, p1-16. 16p.
Subject
*GENE expression
*GENE silencing
*INTESTINAL parasites
*INFLAMMATION
*PERITONEUM
*NEMATODE infections
Language
ISSN
1935-2727
Abstract
Mesocestoides vogae is a cestode parasite of the family Mesocestoididae (order Cyclophyllidea). Its larvae, tetrathyridium, are approximately 1 mm long and 300 μm wide and infect a wide range of host species including humans. Tetrathyridium migrate through the intestinal wall to invade the peritoneal cavity. Despite intestinal penetration by such a large-sized parasite, symptomatic intestinal disorders are not common during the migration period. In this study, the dynamics of tetrathyridia migration and their pathogenicity towards intestinal tissues were examined in mice infected orally with these parasites. Most tetrathyridia were found to migrate through the intestinal wall, moving into the peritoneal cavity or liver 24 to 48 hours after the oral infections. Next, the pathogenicity of tetrathyridium in the intestinal wall was histopathologically evaluated, and tissue injury from tetrathyridium migration was confirmed. Inflammatory foci were observed as tetrathyridium migration tracks from 48 hours after oral infection; however, the number of inflammatory foci had decreased by half more than 48 hours later. Therefore, we examined the gene expression levels of the macrophage driving cytokine, IL-1β, and the eosinophil recruiting chemokine, CCL11, by quantitative reverse-transcriptase PCR. The expression levels of these genes in the infected group were significantly lower than those of the non-infected group at 48 hours post-infection. Although the immunomodulating ability of the excretory-secretory products released from tetrathyridium has been previously shown by in vitro assays, the significance of this ability in their lifecycle has remained unclear. In this study, we discovered that tetrathyridium causes temporal inflammation in the intestinal wall during penetration and large-scale migration in this organ, but tetrathyridium simultaneously suppresses the host's inflammatory gene expression, might to be a strategy that reduces inflammatory responses and increases survival of the parasite. Author summary: Excretory-secretory (ES) products are released by parasitic helminths into their migration sites and/or the intestinal regions they inhabit where parasite and host immune responses interact. ES products are release by a wide range of parasitic helminths, some of which are known to modulate the host's immune system. Some ES products from some cestode parasites are known to reduce the production of pro-inflammatory cytokines from artificially stimulated cells under in vitro conditions. However, the immunomodulatory properties of the ES products have only been observed with in vitro experimental models and the biological consequences of their potential ability to suppress the host's immune system during the parasite's lifecycle and how they affect host–parasite interactions await discovery. Our results show that tetrathyridium, the larval stage of the Mesocestoides vogae cestode, strongly inhibits the host's inflammatory gene expression in the injured intestinal wall, and that the inflammatory hot-spots caused by larval migration disappear almost immediately after mice are orally infected with these parasites. The ability to suppress the host's inflammatory gene expression when larvae migrate through and damage the host's tissues is an effective survival strategy for M. vogae intestinal parasites. [ABSTRACT FROM AUTHOR]