2. Academic Validation
  3. The role of extracellular vesicle fusion with target cells in triggering systemic inflammation

The role of extracellular vesicle fusion with target cells in triggering systemic inflammation

  • Nat Commun. 2024 Feb 7;15(1):1150. doi: 10.1038/s41467-024-45125-1.
Praveen Papareddy 1,  Ines Tapken 2 3 4,  Keshia Kroh 2 5,  Ravi Kiran Varma Bhongir 2,  Milladur Rahman 6,  Maria Baumgarten 2,  Eda Irem Cim 2,  Lilla Györffy 2,  Emanuel Smeds 2,  Ariane Neumann 2,  Srinivas Veerla 7,  Jon Olinder 8,  Henrik Thorlacus 6,  Cecilia Ryden 8,  Eva Bartakova 9,  Michal Holub 9,  Heiko Herwald 10
Affiliations

Affiliations

  • 1 Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden. praveen.papareddy@med.lu.se.
  • 2 Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden.
  • 3 SMATHERIA gGmbH - Non-Profit Biomedical Research Institute, Hannover, Germany.
  • 4 Center for Systems Neuroscience (ZSN), Hannover, Germany.
  • 5 Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands.
  • 6 Section of Surgery, Department of Clinical Sciences, Lund University, Malmö, Sweden.
  • 7 Division of Oncology and Pathology, Lund, Department of Clinical Sciences, Lund University, Lund, Sweden.
  • 8 Division of Infection Medicine, Helsingborg Hospital and Department of Clinical Sciences Helsingborg, Lund University, Lund, Sweden.
  • 9 Department of Infectious Diseases, First Faculty of Medicine, Charles University and Military University Hospital Prague, Praha, Czech Republic.
  • 10 Division of Infection Medicine, Department of Clinical Sciences, Lund University, Lund, Sweden. heiko.hewald@med.lu.se.
PMID: 38326335 DOI: 10.1038/s41467-024-45125-1
Abstract

Extracellular vesicles (EVs) play a crucial role in intercellular communication by transferring bioactive molecules from donor to recipient cells. As a result, EV fusion leads to the modulation of cellular functions and has an impact on both physiological and pathological processes in the recipient cell. This study explores the impact of EV fusion on cellular responses to inflammatory signaling. Our findings reveal that fusion renders non-responsive cells susceptible to inflammatory signaling, as evidenced by increased NF-κB activation and the release of inflammatory mediators. Syntaxin-binding protein 1 is essential for the merge and activation of intracellular signaling. Subsequent analysis show that EVs transfer their functionally active receptors to target cells, making them prone to an otherwise unresponsive state. EVs in complex with their agonist, require no further stimulation of the target cells to trigger mobilization of NF-κB. While receptor antagonists were unable to inhibit NF-κB activation, blocking of the fusion between EVs and their target cells with heparin mitigated inflammation in mice challenged with EVs.

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