Abstract
Maturation of dendritic cells (DCs) induced by pathogen-derived signals via TLRs is a crucial step in the initiation of an adaptive immune response and therefore has to be well controlled. In this study, we demonstrate that oxidized phospholipids (ox-PLs), which are generated during infections, apoptosis, and tissue damage, interfere with DC activation, preventing their maturation. ox-PLs blocked TLR-3- and TLR-4-mediated induction of the costimulatory molecules CD40, CD80, CD83, and CD86, the cytokines IL-12 and TNF, as well as lymphocyte stimulatory capacity. CD40 and TLR-2-mediated cytokine production was also inhibited, whereas up-regulation of costimulatory molecules via these receptors was not affected by ox-PLs. Thus, formation of ox-PLs during the course of an inflammatory response may represent a negative-feedback loop preventing excessive and sustained immune reactions through regulating DC maturation.
Publication types
- Research Support, Non-U.S. Gov't
MeSH terms
- Base Sequence
- CD40 Antigens / metabolism*
- CD40 Ligand / pharmacology
- Cell Differentiation
- Cytokines / biosynthesis
- DNA, Complementary / genetics
- Dendritic Cells / cytology*
- Dendritic Cells / drug effects
- Dendritic Cells / immunology*
- Dendritic Cells / metabolism
- Feedback
- Humans
- In Vitro Techniques
- Inflammation / immunology
- Inflammation / metabolism
- Lipopolysaccharides / pharmacology
- Lymphocyte Activation / drug effects
- Membrane Glycoproteins / metabolism*
- NF-kappa B / metabolism
- Oxidation-Reduction
- Peptidoglycan / pharmacology
- Phosphatidylcholines / pharmacology
- Phospholipids / chemistry
- Phospholipids / immunology*
- Phospholipids / metabolism*
- Poly I-C / pharmacology
- Receptors, Cell Surface / metabolism*
- Signal Transduction / drug effects
- T-Lymphocytes / drug effects
- T-Lymphocytes / immunology
- Toll-Like Receptor 2
- Toll-Like Receptor 3
- Toll-Like Receptor 4
- Toll-Like Receptors
Substances
- CD40 Antigens
- Cytokines
- DNA, Complementary
- Lipopolysaccharides
- Membrane Glycoproteins
- NF-kappa B
- Peptidoglycan
- Phosphatidylcholines
- Phospholipids
- Receptors, Cell Surface
- TLR2 protein, human
- TLR3 protein, human
- TLR4 protein, human
- Toll-Like Receptor 2
- Toll-Like Receptor 3
- Toll-Like Receptor 4
- Toll-Like Receptors
- oxidized-L-alpha-1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine
- CD40 Ligand
- Poly I-C