Platelet Endothelial Cell Adhesion Molecule 1 (CD31) Is Essential for Clostridium perfringens Beta-Toxin Mediated Cytotoxicity in Human Endothelial and Monocytic Cells

Tarek, Basma; Bruggisser, Julia; Cattalani, Filippo; Posthaus, Horst (2021). Platelet Endothelial Cell Adhesion Molecule 1 (CD31) Is Essential for Clostridium perfringens Beta-Toxin Mediated Cytotoxicity in Human Endothelial and Monocytic Cells. Toxins, 13(12), p. 893. MDPI 10.3390/toxins13120893

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Beta toxin (CPB) is a small hemolysin beta pore-forming toxin (β-PFT) produced by Clostridium perfringens type C. It plays a central role in the pathogenesis of necro-hemorrhagic enteritis in young animals and humans via targeting intestinal endothelial cells. We recently identified the membrane protein CD31 (PECAM-1) as the receptor for CPB on mouse endothelial cells. We now assess the role of CD31 in CPB cytotoxicity against human endothelial and monocytic cells using a CRISPR/Cas9 gene knockout and an antibody blocking approach. CD31 knockout human endothelial and monocytic cells were resistant to CPB and CPB oligomers only formed in CD31-expressing cells. CD31 knockout endothelial and monocytic cells could be selectively enriched out of a polyclonal cell population by exposing them to CPB. Moreover, antibody mediated blocking of the extracellular Ig6 domain of CD31 abolished CPB cytotoxicity and oligomer formation in endothelial and monocytic cells. In conclusion, this study confirms the role of CD31 as a receptor of CPB on human endothelial and monocytic cells. Specific interaction with the CD31 molecule can thus explain the cell type specificity of CPB observed in vitro and corresponds to in vivo observations in naturally diseased animals.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Animal Pathology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

Graduate School:

Graduate School for Cellular and Biomedical Sciences (GCB)

UniBE Contributor:

Sayed, Basma Tarek Mohammed Amin; Bruggisser, Julia Maria; Cattalani Tognola, Filippo Manlio and Posthaus, Horst

Subjects:

600 Technology > 630 Agriculture
500 Science > 570 Life sciences; biology

ISSN:

2072-6651

Publisher:

MDPI

Language:

English

Submitter:

Basma Tarek Mohammed Amin Sayed

Date Deposited:

23 Dec 2021 14:28

Last Modified:

01 Mar 2022 11:10

Publisher DOI:

10.3390/toxins13120893

PubMed ID:

34941730

BORIS DOI:

10.48350/162691

URI:

https://boris.unibe.ch/id/eprint/162691

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