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

Janssens, Y.; Debunne, N.; De Spiegeleer, A.; Wynendaele, E.; Planas, M.; Feliu, L.; Quarta, A.; Claes, C.; Van Dam, D.; De Deyn, P. P.; Ponsaerts, P.; Blurton-Jones, M.; De Spiegeleer, B.

doi:10.1101/2020.10.05.327148

bioRxiv · 10.1101/2020.10.05.327148

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

Janssens, Y.·Debunne, N.·De Spiegeleer, A.·Wynendaele, E.·Planas, M.·Feliu, L.·Quarta, A.·Claes, C.·Van Dam, D.·De Deyn, P. P.·Ponsaerts, P.·Blurton-Jones, M.·De Spiegeleer, B.

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Abstract

BackgroundQuorum 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. MethodsGastro-intestinal transport of the peptide is investigated using the in vitro Caco-2 model while transport over the blood-brain barrier is investigated in mice using multiple time regression experiments. Microglial activation is assessed using ELISA, fluorometry, immunoblotting, qPCR and phase-contrast microscopy. In vivo plasma detection and ex vivo metabolization experiments are performed using UHPLC-MS2 and UHPLC-UV/MS, respectively. ResultsPapRIV showed in vitro activating properties of BV-2 microglia cells and was able to cross the in vitro Caco-2 cell model and pass the blood-brain barrier in vivo. In vivo peptide presence was also demonstrated in mouse plasma. The peptide caused induction of IL-6, TNF and ROS expression and increased the fraction of ameboid BV-2 microglia cells in an NF-{kappa}B dependent manner. Different metabolites were identified in serum, of which the main metabolite (DLPFEH) still remained active. ConclusionsPapRIV 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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Janssens, Y., Debunne, N., De Spiegeleer, A., Wynendaele, E., Planas, M., Feliu, L., Quarta, A., Claes, C., Van Dam, D., De Deyn, P. P., Ponsaerts, P., Blurton-Jones, M., De Spiegeleer, B.. 2020-10-05. PapRIV, a BV-2 microglial cell activating quorum sensing peptide. https://doi.org/10.1101/2020.10.05.327148

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