Bacterial Quorum-Sensing Peptides as Immune Modulators Present in Systemic Circulation

Author:

De Spiegeleer Anton1234ORCID,Descamps Amélie13,Govindarajan Srinath45,Coudenys Julie145,Van der borght Kevin3ORCID,Hirmz Hannah3,Van Den Noortgate Nele12,Elewaut Dirk145,De Spiegeleer Bart13,Wynendaele Evelien13ORCID

Affiliation:

1. Translational Research in Immunosenescence, Gerontology and Geriatrics (TRIGG) Group, Ghent University, 9000 Ghent, Belgium

2. Department of Geriatrics, Faculty of Medicine and Health Sciences, Ghent University Hospital, 9000 Ghent, Belgium

3. Drug Quality and Registration (DruQuaR) Group, Faculty of Pharmaceutical Sciences, Ghent University, 9000 Ghent, Belgium

4. VIB Inflammation Research Center, Unit for Molecular Immunology and Inflammation, Ghent University, 9000 Ghent, Belgium

5. Department of Rheumatology, Faculty of Medicine and Health Sciences, Ghent University Hospital, 9000 Ghent, Belgium

Abstract

Quorum-sensing peptides (QSPs) are bacterial peptides traditionally considered only as inter-bacterial communication molecules. Recently, their involvement in microbiome–host interactions influencing host diseases such as cancer and sarcopenia were explored. However, it is still unknown to what extent these peptides have the potential to modulate the immune system. In this proof-of-concept study, we screened 89 QSPs for their potential to induce IL-6 and TNFα in murine splenocytes and J774 macrophages. Confirmatory experiments on the positive screening-hits were conducted using murine splenocytes and human PBMCs of different ages. Finally, to investigate the biological relevance of immunomodulatory QSPs, we analysed plasma in a human cohort for the presence of the immunomodulatory QSP Q010. To do this, we used a newly developed UHPLC-MS/MS method. Our findings indicated that specific QSPs activate immune cells in vitro, with Q007, Q010, Q017 and Q212 being the top four screening hits. Q007 and Q010 were affirmed in subsequent confirmatory experiments using murine splenocytes and human PBMCs. Finally, Q010 was detected in human plasma, demonstrating for the first time the presence of an immunomodulatory QSP in human circulation. In conclusion, our data are the first evidence indicating the potential of biologically relevant quorum-sensing peptides to modulate the immune system.

Funder

Fund Marie-Therese De Lava & Robert Schneider, King Baudouin Foundation, Belgium

Research Foundation-Flanders

Publisher

MDPI AG

Subject

Molecular Biology,Biochemistry

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