Clostridium perfringens Epsilon Toxin Binds to and Kills Primary Human Lymphocytes

epsilon toxin (ETX) is the third most lethal bacterial toxin and has been suggested to be an environmental trigger of multiple sclerosis, an immune-mediated disease of the human central nervous system. However, ETX cytotoxicity on primary human cells has not been investigated. In this article, we de...

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Bibliographic Details
Published in:Toxins 2023-06, Vol.15 (7), p.423
Main Authors: Shetty, Samantha V, Mazzucco, Michael R, Winokur, Paige, Haigh, Sylvia V, Rumah, Kareem Rashid, Fischetti, Vincent A, Vartanian, Timothy, Linden, Jennifer R
Format: Article
Language:English
Subjects:
Apoptosis
Autoimmune diseases
Brain
CD19 antigen
CD4 antigen
CD8 antigen
Central nervous system
Cloning
Clostridium perfringens
Cytotoxicity
epsilon toxin
ETX
Flow cytometry
Gene expression
Immune response
Immune system
Lymphocytes
MAL
MAL gene
Multiple sclerosis
Myelin
myelin and lymphocyte protein
Nervous system
Pathogenesis
Permeability
Proteins
Toxicity
Toxins
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Summary:epsilon toxin (ETX) is the third most lethal bacterial toxin and has been suggested to be an environmental trigger of multiple sclerosis, an immune-mediated disease of the human central nervous system. However, ETX cytotoxicity on primary human cells has not been investigated. In this article, we demonstrate that ETX preferentially binds to and kills human lymphocytes expressing increased levels of the myelin and lymphocyte protein MAL. Using flow cytometry, ETX binding was determined to be time and dose dependent and was highest for CD4+ cells, followed by CD8+ and then CD19+ cells. Similar results were seen with ETX-induced cytotoxicity. To determine if ETX preference for CD4+ cells was related to MAL expression, MAL gene expression was determined by RT-qPCR. CD4+ cells had the highest amount of Mal gene expression followed by CD8+ and CD19+ cells. These data indicate that primary human cells are susceptible to ETX and support the hypothesis that MAL is a main receptor for ETX. Interestingly, ETX bindings to human lymphocytes suggest that ETX may influence immune response in multiple sclerosis.
ISSN:2072-6651
2072-6651
DOI:10.3390/toxins15070423