Bacterial cell wall components as immunomodulators—I. lipopeptides as adjuvants for parenteral and oral immunization

Bessler, Wolfgang G.; Heinevetter, L.; Wiesmüller, Karl‐Heinz; Jung, Günther; Baier, W.; Huber, Michael; Lorenz, Astrid; Esche, Ulrich vor dem; Mittenbühler, K; Hoffmann, Petra

doi:10.1016/s0192-0561(97)00054-4

Cited by 31 publications

(27 citation statements)

References 10 publications

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“…They have long been known as strong cytokine inducers and have recently become the basis for vaccine development, making them key molecules of innate and adaptive immunity (16,55). We show in this study that a host acute-phase protein, LBP, which previously has been known to be a key molecule for pathogen recognition via LPS, LTA, and peptidoglycan, is also crucial for lipoprotein recognition.…”

Section: Discussionmentioning

confidence: 72%

Lipopolysaccharide Binding Protein Binds to Triacylated and Diacylated Lipopeptides and Mediates Innate Immune Responses

Schröder

Heine

Alexander

et al. 2004

The Journal of Immunology

146

118

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LPS binding protein (LBP) is an acute-phase protein synthesized predominantly in the liver of the mammalian host. It was first described to bind LPS of Gram-negative bacteria and transfer it via a CD14-enhanced mechanism to a receptor complex including TLR-4 and MD-2, initiating a signal transduction cascade leading to the release of proinflammatory cytokines. In recent studies, we found that LBP also mediates cytokine induction caused by compounds derived from Gram-positive bacteria, including lipoteichoic acid and peptidoglycan fragments. Lipoproteins and lipopeptides have repeatedly been shown to act as potent cytokine inducers, interacting with TLR-2, in synergy with TLR-1 or -6. In this study, we show that these compounds also interact with LBP and CD14. We used triacylated lipopeptides, corresponding to lipoproteins of Borrelia burgdorferi, mycobacteria, and Escherichia coli, as well as diacylated lipopeptides, corresponding to, e.g., 2-kDa macrophage activating lipopeptide of Mycoplasma spp. Activation of Chinese hamster ovary cells transfected with TLR-2 by both lipopeptides was enhanced by cotransfection of CD14. Responsiveness of human mononuclear cells to these compounds was greatly enhanced in the presence of human LBP. Binding of lipopeptides to LBP as well as competitive inhibition of this interaction by LPS was demonstrated in a microplate assay. Furthermore, we were able to show that LBP transfers lipopeptides to CD14 on human monocytes using FACS analysis. These results support that LBP is a pattern recognition receptor transferring a variety of bacterial ligands including the two major types of lipopeptides to CD14 present in different receptor complexes.

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Section: Discussionmentioning

confidence: 72%

Lipopolysaccharide Binding Protein Binds to Triacylated and Diacylated Lipopeptides and Mediates Innate Immune Responses

Schröder

Heine

Alexander

et al. 2004

The Journal of Immunology

146

118

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“…In addition to LPS a dramatically higher response with respect to TNF was seen with Pam3Cys, a product of Borrelia and of other types of bacteria (12)(13)(14)(15)(16). Also, Zymosan derived from yeast and mycobacterial lipoarabinomannan both induced 2-fold higher levels of specific median immunofluorescence intensity for TNF in the proinflammatory monocytes (data not shown).…”

Section: Cd16mentioning

confidence: 99%

“…The contribution is more pronounced when it comes to Pam3Cys, a compound that represents lipopeptides that are expressed by both Gram-positive and Gram-negative bacteria (12)(13)(14)(15)(16). Hence, lipopeptide-induced cytokines may contribute to any type of bacterial infection.…”

Section: Drmentioning

confidence: 99%

The Proinflammatory CD14+CD16+DR++ Monocytes Are a Major Source of TNF

Belge

Dayyani

Horelt

et al. 2002

The Journal of Immunology

769

630

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In human blood two monocyte populations can be distinguished, i.e., the CD14++CD16−DR+ classical monocytes and the CD14+CD16+DR++ proinflammatory monocytes that account for only 10% of all monocytes. We have studied TNF production in these two types of cells using three-color immunofluorescence and flow cytometry on whole peripheral blood samples stimulated with either LPS or with the bacterial lipopeptide S-(2,3-bis(palmitoyloxy)-(2-RS)-propyl)-N-palmitoyl-(R)-Cys-(S)-Ser-(S)-Lys4-OH,trihydrochloride (Pam3Cys). After stimulation with LPS the median fluorescence intensity for TNF protein was 3-fold higher in the proinflammatory monocytes when compared with the classical monocytes. After stimulation with Pam3Cys they almost exclusively responded showing 10-fold-higher levels of median fluorescence intensity for TNF protein. The median fluorescence intensity for Toll-like receptor 2 cell surface protein was found 2-fold higher on CD14+CD16+DR++ monocytes, which may explain, in part, the higher Pam3Cys-induced TNF production by these cells. When analyzing secretion of TNF protein into the supernatant in PBMCs after depletion of CD16+ monocytes we found a reduction of LPS-induced TNF by 28% but Pam3Cys-induced TNF was reduced by 64%. This indicates that the minor population of CD14+CD16+ monocytes are major producers of TNF in human blood.

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“…Lipopolysaccharide from pathogenic enterobacterial bacteria (eLPS) has been applied in numerous experimental models of infection in which PRRs such as LPS-binding protein (LBP) and CD14 have central roles (2)(3)(4). Lipoprotein is an immunostimulatory PAMP as well (5)(6)(7). Challenge with immunostimulatory Gram-negative or Gram-positive bacterial constituents overactivates the immune system and elicits symptoms that in part are characteristic for sepsis in the course of acute infection (8).…”

mentioning

confidence: 99%

Cellular Recognition of Trimyristoylated Peptide or Enterobacterial Lipopolysaccharide via Both TLR2 and TLR4

Spiller

Dreher

Meng

et al. 2007

Journal of Biological Chemistry

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Bacterial cell wall components as immunomodulators—I. lipopeptides as adjuvants for parenteral and oral immunization

Cited by 31 publications

References 10 publications

Lipopolysaccharide Binding Protein Binds to Triacylated and Diacylated Lipopeptides and Mediates Innate Immune Responses

Lipopolysaccharide Binding Protein Binds to Triacylated and Diacylated Lipopeptides and Mediates Innate Immune Responses

The Proinflammatory CD14+CD16+DR++ Monocytes Are a Major Source of TNF

Cellular Recognition of Trimyristoylated Peptide or Enterobacterial Lipopolysaccharide via Both TLR2 and TLR4

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