The role of integrins in the recognition and response of dendritic cells to biomaterials

Abstract

Biomaterials have the potential to be utilized as immunostimulatory or immunosuppressive delivery agents for biologics. It is hypothesized that this is directed by the ability of a biomaterial to drive dendritic cells (DC) in situ toward an immunostimulatory or an immunosuppressive phenotype, respectively. However, the specific pattern recognition receptors (PRRs) that DCs use to recognize and respond to biomaterials are unknown. From among the many receptors that DCs use to recognize and respond to foreign entities, herein the focus is on integrins. A biomaterial that induces DC maturation, namely poly(lactic-co-glycolic) acid (PLGA), supported increased human monocyte-derived DC adhesion and up-regulation of integrin receptor gene expression, measured via RT-PCR, as compared to culture on tissue culture polystyrene (TCPS). This was not observed for a biomaterial that does not support DC maturation. Through antibody-blocking techniques, the adhesion to both TCPS and PLGA was found to be β 2 integrin dependent and β 1 independent. Significantly, inhibiting β 2-mediated adhesion to biomaterials via blocking antibodies also lowered the level of maturation of DCs (CD86 expression). β 2 integrins (but not β 1) were found localized in biomaterial-adherent DC podosomes and also were found in direct contact with the PLGA surface. Therefore, it appeared that β 2 integrin-mediated adhesion is involved in determining the state of DC maturation on the PLGA surface. DC adhesion to biomaterials may be engaged or avoided to manipulate an immune response to biological component delivered with a biomaterial carrier.