Carbohydrates and
glycoconjugates have been shown to exert pro-inflammatory effects on the dendritic cells (DCs), supporting pathogen-induced innate immunity and antigen processing, as well as immunosuppressive effects in the tolerance to self-
proteins. Additionally, the
innate inflammatory response to implanted
biomaterials has been hypothesized to be mediated by inflammatory cells interacting with adsorbed
proteins, many of which are glycosylated. However, the molecular factors relevant for surface displayed
glycoconjugate modulation of dendritic cell (DC) phenotype are unknown. Thus, in this study, a model system was developed to establish the role of
glycan composition, density, and carrier cationization state on DC response.
Thiol modified
glycans were covalently bound to a model
protein carrier,
maleimide functionalized
bovine serum albumin (BSA), and the number of
glycans per BSA modulated. Additionally, the carrier isoelectric point was scaled from a pI of ∼4.0 to ∼10.0 using
ethylenediamine (EDA). The DC response to the neoglycoconjugates adsorbed to wells of a 384-well plate was determined via a high throughput assay. The underlying trends in DC phenotype in relation to conjugate properties were elucidated via multivariate general linear models. It was found that
glycoconjugates with more than 20
glycans per carrier had the greatest impact on the pro-inflammatory response from DCs, followed by conjugates having an isoelectric point above 9.5. Surfaces displaying terminal α1-2 linked
mannose structures were able to increase the inflammatory DC response to a greater extent than did any other terminal
glycan structure. The results herein can be applied to inform the design of the next generation of combination products and
biomaterials for use in future
vaccines and implanted materials.