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

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 t...

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Main Authors: Shumin Gao, Min Gao, Huanhui Du, Lingyu Li, Xudian An, Yongyu Shi, Xiaoyan Wang, Hua Cong, Bing Han, Chunxue Zhou, Huaiyu Zhou
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Parasites & Vectors
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Online Access:https://doi.org/10.1186/s13071-025-06721-2
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author Shumin Gao
Min Gao
Huanhui Du
Lingyu Li
Xudian An
Yongyu Shi
Xiaoyan Wang
Hua Cong
Bing Han
Chunxue Zhou
Huaiyu Zhou
author_facet Shumin Gao
Min Gao
Huanhui Du
Lingyu Li
Xudian An
Yongyu Shi
Xiaoyan Wang
Hua Cong
Bing Han
Chunxue Zhou
Huaiyu Zhou
author_sort Shumin Gao
collection DOAJ
description 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. Graphical Abstract
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issn 1756-3305
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spelling doaj-art-9d476ec981434f7eb9e99f09bb15b84f2025-08-20T03:01:38ZengBMCParasites & Vectors1756-33052025-03-0118111610.1186/s13071-025-06721-2SARM regulates cell apoptosis and inflammation during Toxoplasma gondii infection through a multistep mechanismShumin Gao0Min Gao1Huanhui Du2Lingyu Li3Xudian An4Yongyu Shi5Xiaoyan Wang6Hua Cong7Bing Han8Chunxue Zhou9Huaiyu Zhou10Department of Pathogen Biology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong UniversityDepartment of Pathogen Biology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong UniversityDepartment of Pathogen Biology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong UniversityDepartment of Pathogen Biology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong UniversityDepartment of Pathogen Biology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong UniversityDepartment of Immunology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong UniversityDepartment of Immunology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong UniversityDepartment of Pathogen Biology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong UniversityDepartment of Pathogen Biology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong UniversityDepartment of Pathogen Biology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong UniversityDepartment of Pathogen Biology, School of Basic Medical Sciences, Cheeloo Medical College, Shandong UniversityAbstract 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. Graphical Abstracthttps://doi.org/10.1186/s13071-025-06721-2SARMToxoplasma gondiiApoptosisInflammationInfection
spellingShingle Shumin Gao
Min Gao
Huanhui Du
Lingyu Li
Xudian An
Yongyu Shi
Xiaoyan Wang
Hua Cong
Bing Han
Chunxue Zhou
Huaiyu Zhou
SARM regulates cell apoptosis and inflammation during Toxoplasma gondii infection through a multistep mechanism
Parasites & Vectors
SARM
Toxoplasma gondii
Apoptosis
Inflammation
Infection
title SARM regulates cell apoptosis and inflammation during Toxoplasma gondii infection through a multistep mechanism
title_full SARM regulates cell apoptosis and inflammation during Toxoplasma gondii infection through a multistep mechanism
title_fullStr SARM regulates cell apoptosis and inflammation during Toxoplasma gondii infection through a multistep mechanism
title_full_unstemmed SARM regulates cell apoptosis and inflammation during Toxoplasma gondii infection through a multistep mechanism
title_short SARM regulates cell apoptosis and inflammation during Toxoplasma gondii infection through a multistep mechanism
title_sort sarm regulates cell apoptosis and inflammation during toxoplasma gondii infection through a multistep mechanism
topic SARM
Toxoplasma gondii
Apoptosis
Inflammation
Infection
url https://doi.org/10.1186/s13071-025-06721-2
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