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十二指肠贾第鞭毛虫特定组合对人肠上皮细胞凋亡和紧密连接破坏的诱导作用:混合感染的影响

Giardia duodenalis assemblage-specific induction of apoptosis and tight junction disruption in human intestinal epithelial cells: effects of mixed infections.

作者信息

Koh Wan Hon, Geurden Thomas, Paget Tim, O'Handley Ryan, Steuart Robert F, Thompson R C Andrew, Buret Andre G

机构信息

School of Veterinary and Biomedical Sciences, Murdoch University, Western Australia.

出版信息

J Parasitol. 2013 Apr;99(2):353-8. doi: 10.1645/GE-3021.1. Epub 2012 Aug 27.

DOI:10.1645/GE-3021.1
PMID:22924932
Abstract

In view of the interest in genotype-specific pathogenesis in Giardia duodenalis , the aim of the present study was to examine the effects of infection with different, or mixed, G. duodenalis assemblages on the integrity of human intestinal epithelia. To that end, human epithelial cells (HCT-8) were cultured and exposed to different G. duodenalis assemblages (A, B, and E) or a combination of these assemblages. Epithelial disruption and apoptosis were evaluated by fluorescent microscopy and apoptotic oligonucleosome quantification. The results indicate that infection with trophozoites disrupts epithelial tight junctions and induces varying degrees of enterocyte apoptosis, depending on the infecting assemblage. All disruptions were caspase-3 dependent and were more pronounced when caused by a non-host specific assemblage. Furthermore, infections by isolates in combination with isolates from another assemblage enhanced the epithelial disruption and apoptosis. Further studies in vitro and in vivo are required to confirm the mechanisms of enhanced pathogenicity of mixed or non-host specific (or both) G. duodenalis infections. Findings in the present study point to the potential pathogenic importance of intra-species polyparasitism in giardiasis.

摘要

鉴于对十二指肠贾第鞭毛虫基因型特异性发病机制的关注,本研究的目的是检测不同或混合的十二指肠贾第鞭毛虫组合感染对人肠上皮完整性的影响。为此,培养人上皮细胞(HCT-8)并使其暴露于不同的十二指肠贾第鞭毛虫组合(A、B和E)或这些组合的混合物中。通过荧光显微镜和凋亡寡核小体定量评估上皮破坏和凋亡。结果表明,滋养体感染会破坏上皮紧密连接,并根据感染的组合诱导不同程度的肠细胞凋亡。所有破坏均依赖于半胱天冬酶-3,并且由非宿主特异性组合引起时更为明显。此外,不同组合的分离株联合感染会增强上皮破坏和凋亡。需要进一步的体外和体内研究来证实混合或非宿主特异性(或两者兼有)十二指肠贾第鞭毛虫感染增强致病性的机制。本研究结果表明种内多重寄生在贾第虫病中具有潜在的致病重要性。

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