Human tetraspanin CD81 facilitates invasion of <i>Salmonella enterica</i> into human epithelial cells
Human CD81 and CD9 are members of the tetraspanin family of proteins characterized by a canonical structure of four transmembrane domains and two extracellular loop domains. Tetraspanins are known as molecular facilitators, which assemble and organize cell surface receptors and partner molecules forming clusters known as tetraspanin-enriched microdomains. They have been implicated to play various biological roles including an involvement in infections with microbial pathogens. Here, we demonstrate an important role of CD81 for the invasion of epithelial cells by <i>Salmonella enterica</i>. We show that the overexpression of CD81 in HepG2 cells enhances invasion of various typhoidal and non-typhoidal <i>Salmonella</i> serovars. Deletion of CD81 by CRISPR/Cas9 in intestinal epithelial cells (C2BBe1 and HT29-MTX-E12) reduces <i>S</i>. Typhimurium invasion. In addition, the effect of human CD81 is species-specific as only human but not rat CD81 facilitates <i>Salmonella</i> invasion. Finally, immunofluorescence microscopy and proximity ligation assay revealed that both human tetraspanins CD81 and CD9 are recruited to the entry site of <i>S</i>. Typhimurium during invasion but not during adhesion to the host cell surface. Overall, we demonstrate that the human tetraspanin CD81 facilitates <i>Salmonella</i> invasion into epithelial host cells.
Authors
- Katrin Ehrhardt (ORCID: https://orcid.org/0000-0003-0471-2008)
- Lisa Laßwitz
- Agnès Wiedemann (ORCID: https://orcid.org/0000-0001-8237-3545)
- Gisa Gerold (ORCID: https://orcid.org/0000-0002-1326-5038)
- Francisco José Zapatero Belinchón (ORCID: https://orcid.org/0000-0002-2751-8411)
- Guntram A. Graßl (ORCID: https://orcid.org/0000-0003-3718-2090)
- Kris Gerard Alvarez
- Thomas Krey (ORCID: https://orcid.org/0000-0002-4548-7241)
- Kumar Nagarathinam (ORCID: https://orcid.org/0000-0003-4200-650X)
- Abdulhadi Suwandi (ORCID: https://orcid.org/0000-0002-1114-8444)
- Katrin Künnemann
- Lisa Goral
Institutions
- Université Toulouse III - Paul Sabatier (FR)
- Inserm (FR)
- École Nationale Vétérinaire de Toulouse (FR)
- Université Fédérale de Toulouse Midi-Pyrénées (FR)
- University of Veterinary Medicine Hannover, Foundation (DE)
- Medizinische Hochschule Hannover (DE)
- Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
- German Center for Infection Research (DE)
- Institut de Recherche en Santé Digestive (FR)
- Centre for Structural Systems Biology (DE)
- Umeå University (SE)
- University of Lübeck (DE)
Publication Details
- Journal
- Virulence
- Published
- 2024-09-06
- DOI
- https://doi.org/10.1080/21505594.2024.2399792
- Citations
- 2
- Primary Topic
- Cell Adhesion Molecules Research
- Type
- article
- Field-Weighted Citation Impact
- 0.77
Funders
- Deutscher Akademischer Austauschdienst
- Deutsche Forschungsgemeinschaft
- Bundesministerium für Bildung und Forschung
- Knut och Alice Wallenbergs Stiftelse
- Medizinischen Hochschule Hannover
- German Academic Exchange Service London