Evidence map›Paper›PMID 40394721›Full record

ArticleParasites & vectors2025

Toxoplasma calcium-dependent protein kinases 3 mediates M1 macrophage polarization by targeting host Arginase-1.

Ran An, Fang Liu, Niuniu Dai, Fangmin Li, Xingyun Liu, Haijian Cai, Lijian Chen, Jian Du

Abstract read
In one paragraph

Article in Parasites & vectors, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

8 authors.

Ran An *Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China.
Fang Liu *Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China.
Niuniu Dai *Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China.
Fangmin LiDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China.
Xingyun LiuDepartment of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China.
Haijian CaiDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China.
Lijian ChenDepartment of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230032, China. chenlijian77@126.com.
Jian DuDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Anhui Medical University, Hefei, 230032, China. dujian@ahmu.edu.cn.

Funding

National Natural Science Foundation of China 82072300
6 · The paper itself

Abstract

backgroundToxoplasma gondii, an obligate intracellular parasite, has developed sophisticated ways to manipulate host immunity, resulting in long-lasting infection and causing serious public health problems in humans and animals. T. gondii type II is the type most frequently associated with human diseases, but the mechanism remains unclear. Toxoplasma calcium-dependent protein kinase 3(CDPK3), a protein located on the T. gondii parasite periphery, is highly expressed in type II strains. Although TgCDPK3 regulates parasite egress from host cells, calcium-based infiltration, and development of tissue cysts, the host target proteins that it modulates are still unclear.

methodsFirstly, mass spectrometry was used to analyze proteins that selectively bind to TgCDPK3. Subsequently, GST (glutathione-s-transferase) pull-down, immunoprecipitation, and immunofluorescence assay were used to confirm the interaction and colocalization between TgCDPK3 and Arginase-1. Western blotting and Argininaseactivity assays were performed to detect the relative levels of endogenous Arginase-1 and inducible nitric oxide synthase (iNOS) in a murine microglial cell line. Fluorescence activated cell sorting (FACS) assays and enzyme-linked immunosorbent assay (ELISA) analysis were performed to confirm the association of interaction between TgCDPK3 and Arginase-1 within an M1/M2-polarized macrophage. Intracellular multiplication assays and plaque assays were performed to test whether the interaction between TgCDPK3 and Arginase-1 affected intercellular parasite growth.

resultsThe interaction between TgCDPK3 and Arginase-1 is functionally correlated and leads to a reduction in Arginase-1 activity, ultimately, contributing to the M1-biased phenotype of the host macrophages, which is related to restraining the proliferation of parasites.

conclusionsOur data showed that CDPK3 mediates M1 macrophage polarization by targeting host Arginase-1, which is beneficial to understanding the mechanism for long term latency establishment of less virulent strains of Toxoplasma.

Indexed as

ArginaseMacrophagesProtein KinasesProtozoan ProteinsToxoplasmaAnimalsCalcium-Calmodulin-Dependent Protein KinasesCell LineHost-Parasite InteractionsHumansMiceNitric Oxide Synthase Type IIArg1 protein, mouseArginaseCalcium-Calmodulin-Dependent Protein KinasesNitric Oxide Synthase Type IIProtein KinasesProtozoan ProteinsArginase-1CDPK3Macrophages polarizationProliferationToxoplasma gondii

Identifiers

PMID40394721
PMCPMC12090600

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.