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The Cytotoxicity of Epsilon Toxin from Clostridium Perfringens on Lymphocytes Is Mediated by MAL Protein Expression

Overview
Journal Mol Cell Biol
Specialty Cell Biology
Date 2018 Jul 11
PMID 29987189
Citations 23
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Abstract

Epsilon toxin (Etx) from is a pore-forming protein that crosses the blood-brain barrier, binds to myelin, and, hence, has been suggested to be a putative agent for the onset of multiple sclerosis, a demyelinating neuroinflammatory disease. Recently, myelin and lymphocyte (MAL) protein has been identified to be a key protein in the cytotoxic effect of Etx; however, the association of Etx with the immune system remains a central question. Here, we show that Etx selectively recognizes and kills only human cell lines expressing MAL protein through a direct Etx-MAL protein interaction. Experiments on lymphocytic cell lines revealed that MAL protein-expressing T cells, but not B cells, are sensitive to Etx and reveal that the toxin may be used as a molecular tool to distinguish subpopulations of lymphocytes. The overall results open the door to investigation of the role of Etx and on inflammatory and autoimmune diseases like multiple sclerosis.

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References
1.
Sonar S, Lal G . Differentiation and Transmigration of CD4 T Cells in Neuroinflammation and Autoimmunity. Front Immunol. 2017; 8:1695. PMC: 5712560. DOI: 10.3389/fimmu.2017.01695. View

2.
Dorca-Arevalo J, Soler-Jover A, Gibert M, Popoff M, Martin-Satue M, Blasi J . Binding of epsilon-toxin from Clostridium perfringens in the nervous system. Vet Microbiol. 2008; 131(1-2):14-25. DOI: 10.1016/j.vetmic.2008.02.015. View

3.
Wioland L, Dupont J, Doussau F, Gaillard S, Heid F, Isope P . Epsilon toxin from Clostridium perfringens acts on oligodendrocytes without forming pores, and causes demyelination. Cell Microbiol. 2014; 17(3):369-88. DOI: 10.1111/cmi.12373. View

4.
Shortt S, Titball R, Lindsay C . An assessment of the in vitro toxicology of Clostridium perfringens type D epsilon-toxin in human and animal cells. Hum Exp Toxicol. 2000; 19(2):108-16. DOI: 10.1191/096032700678815710. View

5.
Chari R, Yeo N, Chavez A, Church G . sgRNA Scorer 2.0: A Species-Independent Model To Predict CRISPR/Cas9 Activity. ACS Synth Biol. 2017; 6(5):902-904. PMC: 5793212. DOI: 10.1021/acssynbio.6b00343. View