Pneumococcal Polysaccharides Interact with Human Dendritic Cells

Abstract

Dendritic cells (DCs) are critical antigen presentation cells whose influence on murine immune responses to polysaccharide antigens has only recently been elucidated. Little is known about human DC-polysaccharide interactions. We set out to study the interaction between human monocyte-derived DCs and pneumococcal capsular polysaccharides (PPS) in vitro. Immature DCs were generated from peripheral blood monocytes and incubated with fluorescein isothiocyanate-labeled PPS type 9N or 14 for assessment of uptake. DCs were exposed to PPS type 1, 6B, 9N, 14, 19F, or 23F in the absence or presence of Escherichia coli lipopolysaccharide (LPS) for assessment of phenotypic DC maturation and cytokine production. PPS were taken up by immature DCs and proceeded to HLA-DR⁺ and lysosome-associated membrane protein-1⁺ late endosomal compartments. Uptake was reduced in the presence of cytochalasin D and wortmannin, suggesting that both cytoskeletal rearrangements and phosphatidylinositol 3-kinase activation may be required for internalization. None of the PPS tested induced DC phenotype changes, maturation, or interleukin-12 (IL-12)/IL-10 production. However, PPS were capable of modulating the response of the DCs to a second signal such as LPS. Exposure of DCs to PPS in the presence of LPS resulted in an altered cytokine balance with significantly increased IL-10 production and reduced IL-12 production compared to LPS alone. This effect was not seen using the control antigen tetanus toxoid. DC-pneumococcus interaction may affect subsequent immune responses to pneumococci, as an altered cytokine balance may have a profound effect on DC-driven T-cell priming.