title: Cultured Mesenchymal Stem Cells Stimulate an Immune Response by Providing Immune Cells with Toll-Like Receptor 2 Ligand.
abstract: Mesenchymal stem cells (MSCs) serve as supporting and regulatory cells, by providing tissues with multiple factors and are also known for their immunosuppressive capabilities. Our laboratory had previously shown that MSCs expressed toll-like receptor (TLR) 2 and are activated by its ligand Pam3Cys. TLR2 is an important component of the innate immune system, as it recognizes bacterial lipopeptides, thus priming a pro-inflammatory immune response. This study showed that Pam3Cys attached extensively to cells of both wild-type and TLR2 deficient cultured MSCs, thus, independently of TLR2. The TLR2 independent binding occurred through the adsorption of the palmitoyl moieties of Pam3Cys. It was further showed that Pam3Cys was transferred from cultured MSCs to immune cells. Moreover, Pam3Cys provided to the immune cells induced a pro-inflammatory response in vitro and in vivo. Overall, it is demonstrated herein that a TLR2 ligand bound to MSCs also through a TLR2 independent mechanism. Furthermore, the ligand incorporated by MSCs is subsequently released to stimulate an immune response both in vitro and in vivo. It is thus suggested that during bacterial infection, stromal cells may retain a reservoir of the TLR2 ligands, in a long-term manner, and release them slowly to maintain an immune response.
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, 234 Herzl Street, Rehovot, 76100, Israel. ada.weinstock@gmail.com.
authors.forename: Ada
authors.initials: A
authors.lastname: Weinstock
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, 234 Herzl Street, Rehovot, 76100, Israel. Meirav.pevsner@weizmann.ac.il.
authors.forename: Meirav
authors.initials: M
authors.lastname: Pevsner-Fischer
authors.affiliation: FACS Unit, Biological Services, Weizmann Institute of Science, 234 Herzl Street, Rehovot, 76100, Israel. Ziv.Porat@weizmann.ac.il.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Porat
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, 234 Herzl Street, Rehovot, 76100, Israel. michael.selitrennik@weizmann.ac.il.
authors.forename: Michael
authors.initials: M
authors.lastname: Selitrennik
authors.affiliation: Department of Molecular Cell Biology, Weizmann Institute of Science, 234 Herzl Street, Rehovot, 76100, Israel. dov.zipori@weizmann.ac.il.
authors.forename: Dov
authors.initials: D
authors.lastname: Zipori
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D007249:Inflammation / Q000276:immunology; D008074:Lipoproteins / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011485:Protein Binding; D051195:Toll-Like Receptor 2 / Q000819:agonists* / Q000235:genetics / Q000276:immunology
chemical_list: D008074:Lipoproteins; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; C061108:N-palmitoyl-S-(2,3-bis(palmitoyloxy)propyl)cysteinyl-seryl-lysyl-lysyl-lysyl-lysine
keywords: Mesenchymal stem cells; Pam3Cys; Toll-like receptor 2