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

IF 3 2区医学 Q1 PARASITOLOGY

Parasites & Vectors Pub Date : 2025-03-12 DOI:10.1186/s13071-025-06721-2

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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引用次数: 0

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.

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来源期刊

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.