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 develop their potent Ag-presenting capacity. Although immature DC can be derived 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 LPS are required for complete maturation and maximum APC function. Because we recently found that microbial lipoproteins can activate monocytes and DC through Toll-like receptor (TLR) 2, we also investigated whether lipoproteins can drive DC maturation. Immature DC were cultured with or without lipoproteins 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 and 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 essential 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 demonstrate that lipopeptides can stimulate DC maturation via TLR2, providing a mechanism by which products of bacteria can participate in the initiation of an immune response.
Hertz
C J
CJ
Division of Dermatology and Pulmonary Medicine, Department of Microbiology and Immunology, and Molecular Biology Institute, University of California School of Medicine, Los Angeles, CA 90095, USA.
Kiertscher
S M
SM
Godowski
P J
PJ
Bouis
D A
DA
Norgard
M V
MV
Roth
M D
MD
Modlin
R L
RL
D001425:Bacterial Outer Membrane Proteins / Q000138:chemical synthesis / Q000494:pharmacology* / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology*; D029721:Drosophila Proteins; D006801:Humans; D016130:Immunophenotyping; D008055:Lipids / Q000502:physiology; D008074:Lipoproteins / Q000138:chemical synthesis / Q000494:pharmacology* / Q000502:physiology; D007959:Lymphocyte Culture Test, Mixed; D008562:Membrane Glycoproteins / Q000502:physiology*; D009169:Mycobacterium tuberculosis / Q000276:immunology; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000502:physiology; D011956:Receptors, Cell Surface / Q000502:physiology*; D012485:Salmonella typhi / Q000276:immunology; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014210:Treponema pallidum / Q000276:immunology
D001425:Bacterial Outer Membrane Proteins; D029721:Drosophila Proteins; D008055:Lipids; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D010455:Peptides; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors