The pathogenic responses elicited during exposure of human intestinal cell line with Giardia duodenalis excretory-secretory products and the potential attributed endocytosis mechanism.

IF 5.5 3区 医学 Q1 IMMUNOLOGY
Xiran Yu, Yongwu Yang, Weining Zhu, Min Liu, Jingxue Wu, Steven M Singer, Wei Li
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引用次数: 0

Abstract

Giardia duodenalis, an important zoonotic protozoan parasite, adheres to host intestinal epithelial cells (IECs) via the ventral disc and causes giardiasis characterized mainly by diarrhea. To date, it remains elusive how excretory-secretory products (ESPs) of Giardia enter IECs and how the cells respond to the entry. Herein, we initially demonstrated that ESPs evoked IEC endocytosis in vitro. We indicated that ESPs contributed vitally in triggering intrinsic apoptosis, pro-inflammatory responses, tight junction (TJ) protein expressional changes, and autophagy in IECs. Endocytosis was further proven to be implicated in those ESPs-triggered IEC responses. Ten predicted virulent excretory-secretory proteins of G. duodenalis were investigated for their capability to activate clathrin/caveolin-mediated endocytosis (CME/CavME) in IECs. Pyridoxamine 5'-phosphate oxidase (PNPO) was confirmed to be an important contributor. PNPO was subsequently verified as a vital promoter in the induction of giardiasis-related IEC apoptosis, inflammation, and TJ protein downregulation. Most importantly, this process seemed to be involved majorly in PNPO-evoked CME pathway, rather than CavME. Collectively, this study identified Giardia ESPs, notably PNPO, as potentially important pathogenic factors during noninvasive infection. It was also noteworthy that ESPs-evoked endocytosis might play a role in triggering giardiasis-inducing cellular regulation. These findings would deepen our understanding about the role of ESPs, notably PNPO, in the pathogenesis of giardiasis and the potential attributed endocytosis mechanism.

人体肠道细胞系与十二指肠贾第虫排泄-分泌产物接触时引发的致病反应以及潜在的内吞机制。
十二指肠贾第虫(Giardia duodenalis)是一种重要的人畜共患原生动物寄生虫,它通过腹盘粘附在宿主肠上皮细胞(IECs)上,引起以腹泻为主要特征的贾第虫病。迄今为止,贾第虫的排泄-分泌产物(ESP)如何进入肠上皮细胞以及细胞如何对这种进入做出反应仍是一个谜。在此,我们初步证明了 ESPs 在体外诱发了 IEC 的内吞作用。我们指出,ESPs 在引发 IECs 内源性凋亡、促炎反应、紧密连接(TJ)蛋白表达变化和自噬方面做出了重要贡献。内吞作用被进一步证明与这些由 ESPs 触发的 IEC 反应有关。研究人员对十种预测的十二指肠球虫毒性排泄分泌蛋白进行了调查,以确定它们在 IECs 中激活凝集素/卡维林介导的内吞(CME/CavME)的能力。经证实,吡多胺-5'-磷酸氧化酶(PNPO)是一个重要的贡献者。PNPO 随后被证实是诱导与包虫病相关的 IEC 细胞凋亡、炎症和 TJ 蛋白下调的重要促进因子。最重要的是,这一过程似乎主要参与了 PNPO 诱导的 CME 途径,而不是 CavME。总之,本研究发现贾第虫ESP,特别是PNPO,可能是非侵入性感染期间的重要致病因素。值得注意的是,ESPs诱发的内吞作用可能在引发贾第虫病的细胞调控中发挥作用。这些发现将加深我们对ESPs(尤其是PNPO)在贾第虫病发病机制中的作用以及潜在的内吞机制的理解。
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来源期刊
CiteScore
10.60
自引率
0.00%
发文量
29
审稿时长
1 months
期刊介绍: Medical Microbiology and Immunology (MMIM) publishes key findings on all aspects of the interrelationship between infectious agents and the immune system of their hosts. The journal´s main focus is original research work on intrinsic, innate or adaptive immune responses to viral, bacterial, fungal and parasitic (protozoan and helminthic) infections and on the virulence of the respective infectious pathogens. MMIM covers basic, translational as well as clinical research in infectious diseases and infectious disease immunology. Basic research using cell cultures, organoid, and animal models are welcome, provided that the models have a clinical correlate and address a relevant medical question. The journal also considers manuscripts on the epidemiology of infectious diseases, including the emergence and epidemic spreading of pathogens and the development of resistance to anti-infective therapies, and on novel vaccines and other innovative measurements of prevention. The following categories of manuscripts will not be considered for publication in MMIM: submissions of preliminary work, of merely descriptive data sets without investigation of mechanisms or of limited global interest, manuscripts on existing or novel anti-infective compounds, which focus on pharmaceutical or pharmacological aspects of the drugs, manuscripts on existing or modified vaccines, unless they report on experimental or clinical efficacy studies or provide new immunological information on their mode of action, manuscripts on the diagnostics of infectious diseases, unless they offer a novel concept to solve a pending diagnostic problem, case reports or case series, unless they are embedded in a study that focuses on the anti-infectious immune response and/or on the virulence of a pathogen.
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