Triacyl-lipopentapeptide adjuvants: TLR2-dependent activation of macrophages and modulation of receptor-mediated cell activation by altering acyl-moieties.
Synthetic lipopeptides derived from bacterial lipoprotein are efficient immunoadjuvants. In vitro they activate antigen presenting cells (APCs) to induce the translocation of nuclear factor kappa B (NF-kappaB) and the activation of further transcription factors. This results in the expression of genes encoding cytokines such as IL-1, IL-6, TNF-alpha and in the release of reactive oxygen/nitrogen intermediates. The molecular structure of microbial products determines TLR specificity and thus their activatory potential and immunoadjuvanticity. In the present study, we investigated the lipopeptide-induced activation of leukocytes at different cellular levels by applying derivatives of a synthetic lipopentapeptide-fatty acid library. Our results show that TLR2 plays a key role for the activation of bone marrow-derived macrophages (BMDMs) by lipopentapeptide derivatives and that the fatty acid composition of the lipopeptides determines their activation potential and TLR specificity.
Müller
Silke D C
SD
Institut für Molekulare Medizin und Zellforschung der Universität, AK Tumorimmunologie/Vakzine, Stefan-Meier-Str. 8, D-79104 Freiburg, Germany.
Müller
Markus R
MR
Huber
Maria
M
Esche Uv
Ulrich v d
Uv
Kirschning
Carsten J
CJ
Wagner
H
H
Bessler
Wolfgang G
WG
Mittenbühler
Klaus
K
D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001426:Bacterial Proteins / Q000737:chemistry; D002460:Cell Line; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000737:chemistry*; D006801:Humans; D066298:In Vitro Techniques; D008074:Lipoproteins / Q000737:chemistry*; D008262:Macrophage Activation / Q000235:genetics / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D014162:Transfection
D000276:Adjuvants, Immunologic; D001426:Bacterial Proteins; D005231:Fatty Acids, Unsaturated; D008074:Lipoproteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D019151:Peptide Library; D010455:Peptides; D011956:Receptors, Cell Surface; C495342:TLR2 protein, human; C493486:Tlr2 protein, mouse; D051195:Toll-Like Receptor 2; D051193:Toll-Like Receptors; D009569:Nitric Oxide; D048049:Extracellular Signal-Regulated MAP Kinases