Platelet Endothelial Cell Adhesion Molecule 1 (CD31) Is Essential for <i>Clostridium perfringens</i> Beta-Toxin Mediated Cytotoxicity in Human Endothelial and Monocytic Cells
Beta toxin (CPB) is a small hemolysin beta pore-forming toxin (β-PFT) produced by <i>Clostridium perfringens</i> 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 identifi...
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MDPI AG
2021-12-01
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| Series: | Toxins |
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| Online Access: | https://www.mdpi.com/2072-6651/13/12/893 |
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| author | Basma Tarek Julia Bruggisser Filippo Cattalani Horst Posthaus |
| author_facet | Basma Tarek Julia Bruggisser Filippo Cattalani Horst Posthaus |
| author_sort | Basma Tarek |
| collection | DOAJ |
| description | Beta toxin (CPB) is a small hemolysin beta pore-forming toxin (β-PFT) produced by <i>Clostridium perfringens</i> 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. |
| first_indexed | 2024-03-10T03:58:03Z |
| format | Article |
| id | doaj.art-71df6482a2404839869b65475d05cc1f |
| institution | Directory Open Access Journal |
| issn | 2072-6651 |
| language | English |
| last_indexed | 2024-03-10T03:58:03Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Toxins |
| spelling | doaj.art-71df6482a2404839869b65475d05cc1f2023-11-23T10:51:03ZengMDPI AGToxins2072-66512021-12-01131289310.3390/toxins13120893Platelet Endothelial Cell Adhesion Molecule 1 (CD31) Is Essential for <i>Clostridium perfringens</i> Beta-Toxin Mediated Cytotoxicity in Human Endothelial and Monocytic CellsBasma Tarek0Julia Bruggisser1Filippo Cattalani2Horst Posthaus3Institute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3012 Bern, SwitzerlandInstitute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3012 Bern, SwitzerlandInstitute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3012 Bern, SwitzerlandInstitute of Animal Pathology, Vetsuisse Faculty, University of Bern, 3012 Bern, SwitzerlandBeta toxin (CPB) is a small hemolysin beta pore-forming toxin (β-PFT) produced by <i>Clostridium perfringens</i> 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.https://www.mdpi.com/2072-6651/13/12/893PECAM-1CD31<i>Clostridium perfringens</i>beta-toxinpore forming toxinmembrane receptor |
| spellingShingle | Basma Tarek Julia Bruggisser Filippo Cattalani Horst Posthaus Platelet Endothelial Cell Adhesion Molecule 1 (CD31) Is Essential for <i>Clostridium perfringens</i> Beta-Toxin Mediated Cytotoxicity in Human Endothelial and Monocytic Cells Toxins PECAM-1 CD31 <i>Clostridium perfringens</i> beta-toxin pore forming toxin membrane receptor |
| title | Platelet Endothelial Cell Adhesion Molecule 1 (CD31) Is Essential for <i>Clostridium perfringens</i> Beta-Toxin Mediated Cytotoxicity in Human Endothelial and Monocytic Cells |
| title_full | Platelet Endothelial Cell Adhesion Molecule 1 (CD31) Is Essential for <i>Clostridium perfringens</i> Beta-Toxin Mediated Cytotoxicity in Human Endothelial and Monocytic Cells |
| title_fullStr | Platelet Endothelial Cell Adhesion Molecule 1 (CD31) Is Essential for <i>Clostridium perfringens</i> Beta-Toxin Mediated Cytotoxicity in Human Endothelial and Monocytic Cells |
| title_full_unstemmed | Platelet Endothelial Cell Adhesion Molecule 1 (CD31) Is Essential for <i>Clostridium perfringens</i> Beta-Toxin Mediated Cytotoxicity in Human Endothelial and Monocytic Cells |
| title_short | Platelet Endothelial Cell Adhesion Molecule 1 (CD31) Is Essential for <i>Clostridium perfringens</i> Beta-Toxin Mediated Cytotoxicity in Human Endothelial and Monocytic Cells |
| title_sort | platelet endothelial cell adhesion molecule 1 cd31 is essential for i clostridium perfringens i beta toxin mediated cytotoxicity in human endothelial and monocytic cells |
| topic | PECAM-1 CD31 <i>Clostridium perfringens</i> beta-toxin pore forming toxin membrane receptor |
| url | https://www.mdpi.com/2072-6651/13/12/893 |
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