Characteristics of inflammatory reactions during development of liver abscess in hamsters inoculated with Entamoeba nuttalli

Abstract

BackgroundEntamoeba nuttalli is an intestinal protozoan with pathogenic potential that can cause amebic liver abscess. It is highly prevalent in wild and captive macaques. Recently, cysts were detected in a caretaker of nonhuman primates in a zoo, indicating that E. nuttalli may be a zoonotic pathogen. Therefore, it is important to evaluate the pathogenicity of E. nuttalli in detail and in comparison with that of E. histolytica.Methodology/Principal findingsTrophozoites of E. nuttalli GY4 and E. histolytica SAW755 strains were inoculated into liver of hamsters. Expression levels of proinflammatory factors of hamsters and virulence factors from E. histolytica and E. nuttalli were compared between the two parasites. Inoculations with trophozoites of E. nuttalli resulted in an average necrotic area of 24% in liver tissue in 7 days, whereas this area produced by E. histolytica was nearly 50%. Along with the mild liver tissue damage induced by E. nuttalli, expression levels of proinflammatory factors (TNF-α, IL-6 and IL-1β) and amebic virulence protein genes (lectins, cysteine proteases and amoeba pores) in local tissues were lower with E. nuttalli in comparison with E. histolytica. In addition, M2 type macrophages were increased in E. nuttalli-induced amebic liver abscesses in the late stage of disease progression and lysate of E. nuttalli trophozoites induced higher arginase expression than E. histolytica in vitro.Conclusions/SignificanceThe results show that differential secretion of amebic virulence proteins during E. nuttalli infection triggered lower levels of secretion of various cytokines and had an impact on polarization of macrophages towards a M1/M2 balance. However, regardless of the degree of macrophage polarization, there is unambiguous evidence of an intense acute inflammatory reaction in liver of hamsters after infection by both Entamoeba species.

Whole genome sequencing of Entamoeba nuttalli reveals mammalian host-related molecular signatures and a novel octapeptide-repeat surface protein

“…nuttalli have been reported in an Abyssinian colobus and Geoffroy’s spider monkey in a zoo [95,96]; and severe inflammatory reactions have been found in livers of hamsters inoculated experimentally with E . nuttalli , which indicates pathogenicity for these host species [12,15,17,97]. These findings suggest that the surface molecules of E .…”

Molecular identification and seasonal prevalence of Entamoeba in wild Tibetan macaques (Macaca thibetana) from Mount Gongga, China

“…In recent years, E. nuttalli has received attention as a potentially pathogenic and zoonotic parasite (Tachibana et al, 2009;Guan et al, 2018) (Levecke et al, 2015). Previous studies on E. nuttalli suggested that the genetic diversity of tRNA-STRs was much higher than that of the SSU rRNA gene and was signi cantly correlated with the genetic diversity of the host (Wei et al, 2018;Feng et al, 2019;Mon et al, 2021).…”

“…E. nuttalli is generally considered a potentially pathogenic parasite that is closely related to E. histolytica in phylogeny, its rst discovery was in non-human primates (NHPs) (Tachibana et al, 2007). Laboratory studies have found that mice inoculated with E. nuttalli developed severe in ammatory reactions and liver abscesses, which were similar to the E. histolytica infection (Tachibana et al, 2009;Guan et al, 2018). In China, E. nuttalli has only been found in wild and captive NHPs, but a previous study reported its asymptomatic infection in a zoo keeper of NHPs in Europe, therefore, E. nuttalli is considered a potential zoonotic parasite.…”

Group 2 Innate Lymphoid Cells Exacerbate Amebic Liver Abscess in Mice

“…It was reported that IL-5 increased the number of alternatively activated macrophages and fibroblasts ( Reiman et al., 2006 ). In a hamster model of ALA caused by E. nuttalli, which is highly prevalent in macaques, alternatively activated macrophages were increased in the liver in the late stage of abscess progression ( Guan et al., 2018 ). Thus, alternatively activated macrophages augmented by IL-5 might contribute to the pathology of ALA caused by E. histolytica .…”