Microbial lipopeptides stimulate dendritic cell maturation via toll-like receptor 2

The ability of dendritic cells (DC) to initiate immune responses in naive T cells is dependent upon a maturation process that allows the cells to deve lop their potent Ag-presenting capacity. Although immature DC can be derive d in vitro by treatment of peripheral blood monocytes with GM-CSF and IL-4, additional signals such as those provided by TNF-alpha, CD40 ligand, or LP S are required for complete maturation and maximum APC function. Because we recently found that microbial lipoproteins can activate monocytes and DC t hrough Tall-like receptor (TLR) 2, we also investigated whether lipoprotein s can drive DC maturation. Immature DC were cultured with or without lipopr oteins and were monitored for expression of cell surface markers indicative of maturation. Stimulation with lipopeptides increased expression of CD83, MHC class II, CD80, CD86, CD54, and CD58, and decreased CD32 expression an d endocytic activity; these lipopeptide-matured DC also displayed enhanced T cell stimulatory capacity in MLR, as measured by T cell proliferation and IFN-gamma secretion, The lipid moiety of the lipopeptide was found to be e ssential for induction of maturation. Preincubation of maturing DC with an anti-TLR2 blocking Ab before addition of lipopeptide blocked the phenotypic and functional changes associated with DC maturation. These results demons trate that lipopeptides can stimulate DC maturation via TLR2, providing a m echanism by which products of bacteria can participate in the initiation of an immune response. The Journal of Immunology, 2001, 166: 2413-2450.