title: The role of multiple toll-like receptor signalling cascades on interactions between biomedical polymers and dendritic cells.
abstract: Biomaterials are used in several health-related applications ranging from tissue regeneration to antigen-delivery systems. Yet, biomaterials often cause inflammatory reactions suggesting that they profoundly alter the homeostasis of host immune cells such as dendritic cells (DCs). Thus, there is a major need to understand how biomaterials affect the function of these cells. In this study, we have analysed the influence of chemically and physically diverse biomaterials on DCs using several murine knockouts. DCs can sense biomedical polymers through a mechanism, which involves multiple TLR/MyD88-dependent signalling pathways, in particular TLR2, TLR4 and TLR6. TLR-biomaterial interactions induce the expression of activation markers and pro-inflammatory cytokines and are sufficient to confer on DCs the ability to activate antigen-specific T cells. This happens through a direct biomaterial-DC interaction although, for degradable biomaterials, soluble polymer molecules can also alter DC function. Finally, the engagement of TLRs by biomaterials profoundly alters DC adhesive properties. Our findings could be useful for designing structure-function studies aimed at developing more bioinert materials. Moreover, they could also be exploited to generate biomaterials for studying the molecular mechanisms of TLR signalling and DC activation aiming at fine-tuning desired and pre-determined immune responses.
authors.affiliation: Institute of Biomedical Engineering, Department of Cell Biology, Universitätsklinikum Aachen, Rheinisch-Westfälische Technische Hochschule (RWTH), Pauwelsstrasse, 30, D-52074 Aachen, Germany.
authors.forename: Behnaz
authors.initials: B
authors.lastname: Shokouhi
authors.forename: Cevayir
authors.initials: C
authors.lastname: Coban
authors.forename: Vasif
authors.initials: V
authors.lastname: Hasirci
authors.forename: Erkin
authors.initials: E
authors.lastname: Aydin
authors.forename: Anandhan
authors.initials: A
authors.lastname: Dhanasingh
authors.forename: Nian
authors.initials: N
authors.lastname: Shi
authors.forename: Shohei
authors.initials: S
authors.lastname: Koyama
authors.forename: Shizuo
authors.initials: S
authors.lastname: Akira
authors.forename: Martin
authors.initials: M
authors.lastname: Zenke
authors.forename: Antonio S
authors.initials: AS
authors.lastname: Sechi
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000737:chemistry / Q000378:metabolism*; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology; D051216:Toll-Like Receptor 6 / Q000235:genetics / Q000276:immunology; D051193:Toll-Like Receptors / Q000235:genetics / Q000276:immunology*
chemical_list: D001672:Biocompatible Materials; D053594:Myeloid Differentiation Factor 88; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051216:Toll-Like Receptor 6; D051193:Toll-Like Receptors