Targeting with oligomannose-coated liposomes promotes maturation and splenic trafficking of dendritic cells in the peritoneal cavity.

摘要

In previous studies, we have shown that oligomannose-coated liposomes (OMLs) have a strong adjuvant effect in inducing T-helper 1 (Th1) immune responses and cytotoxic T cells specific for the encased antigen. In the present study, we demonstrate that preferential uptake of OMLs by DCs and subsequent DC maturation and splenic trafficking may be correlated with the adjuvant effect of OMLs. About 3% of resting murine peritoneal cells are CD11b(dull)CD11c(+) cells, which express MHC class II and CD86, and about 30% are CD11b(high)CD11c(-) cells, which express F4/80 and CD14. This indicates that these cells are resident peritoneal DCs and monocytes/macrophages, respectively. Both types of cells rapidly took up OMLs in the peritoneal cavity, but only CD11b(dull)CD11c(+) cells produced interleukin (IL)-12 in response to OML uptake. IL-6 was not produced by either type of cells. The expression levels of CD205 and CCR7, which are markers of cell maturity in murine DCs, were upregulated in CD11b(dull)CD11c(+) cells obtained from OML-treated mice. In addition, CD11b(dull)CD11c(+) cells with ingested OMLs were found in the spleen 18 h after intraperitoneal administration of OMLs. These results indicate that OMLs can be used as a vehicle for delivery of antigens to DCs and as an adjuvant to promote DC maturation, activation, and trafficking into lymphoid organs, thereby eliciting a Th1 immune response.