2026, 24 301.

Extracellular vesicles derived from Enterococcus faecalis: inflammatory activation does not require internalization

Guevara, Marlon A. G. | Kardani, Arefeh | Schomisch, Annika | Rasheed, Sari | Mashayekhi, Vida | Saccon, Emely | Abdukarimov, Nurzhan | Kirilov, Nikolay K. | Junker, Sabryna | Weiss, Agnes-Valencia | Koch, Marcus | Gasparaoni, Gilles | Schneider, Marc | Schulze-Hentrisch, Julia | Bischoff, Markus | Becker, Sören L. | Müller, Rolf | Yildiz, Daniela | Fuhrmann, Gregor | Staufer, Oskar | Hoppstädter, Jessica | Kiemer, Alexandra K.

Enterococcus faecalis is a commensal bacterium in the human gut, but it can also cause life-threatening diseases, especially serious hospital-acquired infections. Bacteria release particles called extracellular vesicles (EVs), which help them interact and communicate with other cells, including bacteria and human cells. However, it is unclear how EVs produced by E. faecalis (Ef-EVs) affect the host immune system. In this study, we investigated how Ef-EVs affect immune and endothelial cells. We found that Ef-EVs activate inflammatory responses through a receptor on the cell surface, without the need to be taken up by the cells. In addition, Ef-EVs altered the metabolism of immune cells, shifting them towards a state that supports inflammation. These findings highlight a previously underexplored mechanism by which Gram-positive bacterial EVs can shape host immunity and cellular metabolism, thereby advancing our understanding of host-pathogen interactions.

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