SARM regulates cell apoptosis and inflammation during Toxoplasma gondii infection through a multistep mechanism.

IF 3 2区 医学 Q1 PARASITOLOGY
Shumin Gao, Min Gao, Huanhui Du, Lingyu Li, Xudian An, Yongyu Shi, Xiaoyan Wang, Hua Cong, Bing Han, Chunxue Zhou, Huaiyu Zhou
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Abstract

Background: The sterile alpha and HEAT/Armadillo motif (SARM) is the fifth Toll-like receptor (TLR) adaptor protein containing the Toll/interleukin-1 receptor (TIR) domain, which is highly enriched in the brain. Toxoplasma gondii (T. gondii) is an obligate intracellular parasitic protozoan that causes zoonotic toxoplasmosis, resulting in threats to human health, such as brain damage. Previous studies have shown that SARM plays crucial roles in cell death and triggers specific transcription programs of innate immunity in response to cell stress, viral, and bacterial infections. However, whether SARM is involved in T. gondii infection remains unclear.

Methods: In this report, quantitative real-time polymerase chain reaction (qPCR), western blot, flow cytometry, ethynyldeoxyuridine (EdU) assay, and enzyme-linked immunosorbent assay (ELISA) were used to explore the relationship between SARM and T. gondii.

Results: Here, we showed that T. gondii infection increased the expression of SARM in vitro and in vivo. SARM induced cell apoptosis during T. gondii infection, activating the mitochondrial apoptotic pathway, the endoplasmic reticulum stress (ER) pathway, and the mitogen-activated protein kinase (MAPK) signaling pathway, and prompting the production of reactive oxygen species (ROS). Furthermore, SARM participated in the regulation of the inflammatory response through the nod-like receptor pyrin domain 3 (NLRP3) inflammasome signaling pathway during T. gondii in vitro infection.

Conclusions: These results elucidate the relationship between SARM and T. gondii infection, suggesting that SARM may represent a potential target for T. gondii control.

SARM通过多步骤机制调节刚地弓形虫感染过程中的细胞凋亡和炎症。
背景:无菌α和HEAT/犰狳基序(SARM)是含有Toll/白细胞介素-1受体(TIR)结构域的第五种Toll样受体(TLR)接头蛋白,在大脑中高度富集。刚地弓形虫(弓形虫)是一种专性细胞内寄生原生动物,可引起人畜共患弓形虫病,对人类健康造成威胁,如脑损伤。先前的研究表明,SARM在细胞死亡中起着至关重要的作用,并在细胞应激、病毒和细菌感染的反应中触发先天免疫的特异性转录程序。然而,SARM是否与弓形虫感染有关尚不清楚。方法:采用实时定量聚合酶链反应(qPCR)、western blot、流式细胞术、乙基脱氧尿苷(EdU)、酶联免疫吸附试验(ELISA)等方法,探讨SARM与弓形虫的关系。结果:我们发现弓形虫感染使体内和体外的SARM表达增加。SARM在弓形虫感染过程中诱导细胞凋亡,激活线粒体凋亡通路、内质网应激(ER)通路和丝裂原活化蛋白激酶(MAPK)信号通路,促进活性氧(ROS)的产生。此外,在弓形虫体外感染过程中,SARM通过淋巴结样受体pyrin结构域3 (NLRP3)炎性小体信号通路参与了炎症反应的调控。结论:这些结果阐明了SARM与弓形虫感染之间的关系,提示SARM可能是控制弓形虫的潜在靶点。
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来源期刊
Parasites & Vectors
Parasites & Vectors 医学-寄生虫学
CiteScore
6.30
自引率
9.40%
发文量
433
审稿时长
1.4 months
期刊介绍: Parasites & Vectors is an open access, peer-reviewed online journal dealing with the biology of parasites, parasitic diseases, intermediate hosts, vectors and vector-borne pathogens. Manuscripts published in this journal will be available to all worldwide, with no barriers to access, immediately following acceptance. However, authors retain the copyright of their material and may use it, or distribute it, as they wish. Manuscripts on all aspects of the basic and applied biology of parasites, intermediate hosts, vectors and vector-borne pathogens will be considered. In addition to the traditional and well-established areas of science in these fields, we also aim to provide a vehicle for publication of the rapidly developing resources and technology in parasite, intermediate host and vector genomics and their impacts on biological research. We are able to publish large datasets and extensive results, frequently associated with genomic and post-genomic technologies, which are not readily accommodated in traditional journals. Manuscripts addressing broader issues, for example economics, social sciences and global climate change in relation to parasites, vectors and disease control, are also welcomed.
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