PapRIV, a BV-2 microglial cell activating quorum sensing peptide

  • Sci Rep. 2021 May 21;11(1):10723. doi: 10.1038/s41598-021-90030-y.
Yorick Janssens  1 ,  Nathan Debunne  1 ,  Anton De Spiegeleer  1  2  3 ,  Evelien Wynendaele  1 ,  Marta Planas  4 ,  Lidia Feliu  4 ,  Alessandra Quarta  5  6 ,  Christel Claes  7 ,  Debby Van Dam  8  9 ,  Peter Paul De Deyn  8  9 ,  Peter Ponsaerts  5  6 ,  Matthew Blurton-Jones  7  10  11 ,  Bart De Spiegeleer  12
Affiliations
  • 1. Drug Quality and Registration (DruQuaR) Group, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium.
  • 2. Department of Geriatrics, Faculty of Medicine and Health Sciences, Ghent University Hospital, Ghent, Belgium.
  • 3. Unit for Molecular Immunology and Inflammation, VIB-Center for Inflammation Research, Zwijnaarde, Belgium.
  • 4. LIPPSO, University of Girona, Girona, Spain.
  • 5. Laboratory of Experimental Hematology, University of Antwerp, Wilrijk, Belgium.
  • 6. Vaccine and Infectious Disease Institute (Vaxinfectio), University of Antwerp, Wilrijk, Belgium.
  • 7. Sue and Bill Gross Stem Cell Research Center, University of California, Irvine, CA, 92696, USA.
  • 8. Laboratory of Neurochemistry and Behavior, Institute Born-Bunge, University of Antwerp, Wilrijk, Belgium.
  • 9. Department of Neurology and Alzheimer Center, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
  • 10. Department of Neurobiology and Behavior, University of California, Irvine, CA, 92697, USA.
  • 11. Institute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, 92696, USA.
  • 12. Drug Quality and Registration (DruQuaR) Group, Faculty of Pharmaceutical Sciences, Ghent University, Ghent, Belgium. [email protected].
PMID: 34021199 DOI: 10.1038/s41598-021-90030-y
Abstract

Quorum sensing peptides (QSPs) are Bacterial peptides produced by Gram-positive bacteria to communicate with their peers in a cell-density dependent manner. These peptides do not only act as interbacterial communication signals, but can also have effects on the host. Compelling evidence demonstrates the presence of a gut-brain axis and more specifically, the role of the gut microbiota in microglial functioning. The aim of this study is to investigate microglial activating properties of a selected QSP (PapRIV) which is produced by Bacillus cereus species. PapRIV showed in vitro activating properties of BV-2 microglia cells and was able to cross the in vitro Caco-2 cell model and reach the brain. In vivo peptide presence was also demonstrated in mouse plasma. The peptide caused induction of IL-6, TNFα and ROS expression and increased the fraction of ameboid BV-2 microglia cells in an NF-κB dependent manner. Different metabolites were identified in serum, of which the main metabolite still remained active. PapRIV is thus able to cross the gastro-intestinal tract and the blood-brain barrier and shows in vitro activating properties in BV-2 microglia cells, hereby indicating a potential role of this quorum sensing peptide in gut-brain interaction.

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