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利用蛋白质组学方法鉴定弓形虫感染后调节的宿主细胞蛋白:分子原理。

Host cell proteins modulated upon Toxoplasma infection identified using proteomic approaches: a molecular rationale.

机构信息

Department of Parasitology and Mycology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Infectious and Tropical Diseases Group (e-INTRO), Institute of Biomedical Research of Salamanca-Research Center for Tropical Diseases at the University of Salamanca (IBSAL-CIETUS), Faculty of Pharmacy, University of Salamanca, 37008, Salamanca, Spain.

出版信息

Parasitol Res. 2022 Jul;121(7):1853-1865. doi: 10.1007/s00436-022-07541-4. Epub 2022 May 13.

Abstract

Toxoplasma gondii is a pathogenic protozoan parasite belonging to the apicomplexan phylum that infects the nucleated cells of warm-blooded hosts leading to an infectious disease known as toxoplasmosis. Apicomplexan parasites such as T. gondii can display different mechanisms to control or manipulate host cells signaling at different levels altering the host subcellular genome and proteome. Indeed, Toxoplasma is able to modulate host cell responses (especially immune responses) during infection to its advantage through both structural and functional changes in the proteome of different infected cells. Consequently, parasites can transform the invaded cells into a suitable environment for its own replication and the induction of infection. Proteomics as an applicable tool can identify such critical proteins involved in pathogen (Toxoplasma)-host cell interactions and consequently clarify the cellular mechanisms that facilitate the entry of pathogens into host cells, and their replication and transmission, as well as the central mechanisms of host defense against pathogens. Accordingly, the current paper reviews several proteins (identified using proteomic approaches) differentially expressed in the proteome of Toxoplasma-infected host cells (macrophages and human foreskin fibroblasts) and tissues (brain and liver) and highlights their plausible functions in the cellular biology of the infected cells. The identification of such modulated proteins and their related cell impact (cell responses/signaling) can provide further information regarding parasite pathogenesis and biology that might lead to a better understanding of therapeutic strategies and novel drug targets.

摘要

刚地弓形虫是一种致病性的顶复门原虫寄生虫,感染温血宿主有核细胞,导致一种称为弓形体病的传染病。顶复门寄生虫,如刚地弓形虫,可以通过不同感染细胞的蛋白质组的结构和功能变化,在不同水平上控制或操纵宿主细胞信号,改变宿主亚细胞基因组和蛋白质组。事实上,刚地弓形虫能够通过在蛋白质组水平上的结构和功能改变,在感染过程中调节宿主细胞的反应(尤其是免疫反应),使其受益。因此,寄生虫可以将入侵的细胞转化为适合自身复制和诱导感染的环境。蛋白质组学作为一种适用的工具,可以识别参与病原体(刚地弓形虫)-宿主细胞相互作用的关键蛋白质,并阐明促进病原体进入宿主细胞及其复制和传播的细胞机制,以及宿主防御病原体的中心机制。因此,本文综述了几种在刚地弓形虫感染的宿主细胞(巨噬细胞和人包皮成纤维细胞)和组织(脑和肝)的蛋白质组中差异表达的蛋白质(通过蛋白质组学方法鉴定),并强调了它们在感染细胞的细胞生物学中可能的功能。这些调节蛋白及其相关细胞反应(细胞信号)的鉴定,可以提供有关寄生虫发病机制和生物学的进一步信息,可能有助于更好地理解治疗策略和新的药物靶点。

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