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Published on: October 18, 2019
The Cytotoxicity of Epsilon Toxin from Clostridium perfringens on Lymphocytes Is Mediated by MAL Protein Expression
Marta Blanch1,2,3, Jonatan Dorca-Arévalo1,2,3, Anna Not1
1Laboratory of Cellular and Molecular Neurobiology, Department of Pathology and Experimental Therapeutics, Campus of Bellvitge, University of Barcelona, Hospitalet de Llobregat, Barcelona, Spain.
Abstract:
Epsilon toxin (Etx) from Clostridium perfringens 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 Clostridium perfringens on inflammatory and autoimmune diseases like multiple sclerosis.
Insights
Epsilon toxin (Etx) from Clostridium perfringens targets human cells expressing myelin and lymphocyte (MAL) protein. This toxin selectively affects T cells, suggesting its potential role in autoimmune diseases like multiple sclerosis.
Area of Science:
- Neuroimmunology
- Microbial Pathogenesis
- Cell Biology
Background:
- Epsilon toxin (Etx) from Clostridium perfringens is a pore-forming protein implicated in neurological disorders.
- Etx crosses the blood-brain barrier and binds to myelin, suggesting a role in demyelinating diseases like multiple sclerosis.
- Myelin and lymphocyte (MAL) protein is a recently identified key factor in Etx's cytotoxic effects, but Etx's immune system association is unclear.
Purpose of the Study:
- To investigate the direct interaction between Epsilon toxin (Etx) and myelin and lymphocyte (MAL) protein.
- To determine the selectivity of Etx for human cell lines expressing MAL protein.
- To explore the potential of Etx as a tool for distinguishing lymphocyte subpopulations.
Main Methods:
- Utilized human cell lines expressing MAL protein to assess Etx cytotoxicity.
- Performed direct protein interaction assays between Etx and MAL protein.
- Conducted experiments on lymphocytic cell lines (T cells and B cells) to evaluate Etx sensitivity.
Main Results:
- Epsilon toxin (Etx) selectively recognizes and induces cell death in human cell lines expressing MAL protein.
- A direct interaction between Etx and MAL protein was confirmed.
- MAL protein-expressing T cells are sensitive to Etx, while B cells are not.
- Etx demonstrates potential as a molecular tool to differentiate lymphocyte subpopulations.
Conclusions:
- Etx exhibits specific binding and cytotoxic activity mediated by MAL protein.
- Etx's selective toxicity towards T cells suggests a role in immune system modulation.
- These findings open avenues for researching Clostridium perfringens' involvement in inflammatory and autoimmune diseases, including multiple sclerosis.
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