Interaction of lipoteichoic acid and CpG-DNA during activation of innate immune cells

Alexander H. Dalpke, Markus Frey, Siegfried Morath, Thomas Hartung, Klaus Heeg

Research output: Contribution to journalArticle

Abstract

The innate immune system recognizes pathogen-associated molecular patterns (PAMP) to cope with evolving infections. Toll-like receptors (TLRs) play a pivotal role in recognition of PAMPs. In the course of infection not a single but rather a full panel of different microbial components interacts with distinct TLRs simultaneously. Only limited information is available on effects of combinations of TLR agonists. Here, we have analyzed the effects of lipoteichoic acid (LTA), CpG-DNA and combinations thereof on innate immune cells in vitro. Although proinflammatory cytokines like TNF-α were induced by these agonists in quite similar amounts, CpG DNA was superior in its potency to induce IL-12p40 reflecting important differences in the biological valence of LTA and CpG-DNA. When given in combination, LTA and CpG-DNA were additive in induction of TNF-α, IL-6 and nitric oxide in RAW 264 macrophages, peritoneal macrophages and dendritic cells. Additive effects were also observed in regard to TNF-α mRNA. In contrast, LTA suppressed IL12p40 secretion induced by CpG-DNA in AW cells and peritoneal macrophages but not in dendritic cells. Intracellular signal cascades (NFκB and p38 MAP kinase) showed additive effects after simultaneous triggering. mRNA expression of TLRs showed only minor regulation after CpG or LTA application and thus does not account for the additive/suppressive effects observed. These results indicate that the consequences of interaction of innate immune cells with microbial pattern depend on the responding cell type and might be differential for certain effector mechanisms. Thus, the pathogen-characteristic panel of TLR ligands will induce pathogen-specific innate responses decisive for the inflammatory reactions.

Original languageEnglish (US)
Pages (from-to)392-407
Number of pages16
JournalImmunobiology
Volume206
Issue number4
StatePublished - 2002
Externally publishedYes

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Toll-Like Receptors
DNA
Peritoneal Macrophages
Dendritic Cells
Interleukin-12 Subunit p40
Messenger RNA
p38 Mitogen-Activated Protein Kinases
Infection
Immune System
Interleukin-6
Nitric Oxide
Macrophages
lipoteichoic acid
Cytokines
Ligands
Pathogen-Associated Molecular Pattern Molecules

ASJC Scopus subject areas

  • Immunology

Cite this

Dalpke, A. H., Frey, M., Morath, S., Hartung, T., & Heeg, K. (2002). Interaction of lipoteichoic acid and CpG-DNA during activation of innate immune cells. Immunobiology, 206(4), 392-407.

Interaction of lipoteichoic acid and CpG-DNA during activation of innate immune cells. / Dalpke, Alexander H.; Frey, Markus; Morath, Siegfried; Hartung, Thomas; Heeg, Klaus.

In: Immunobiology, Vol. 206, No. 4, 2002, p. 392-407.

Research output: Contribution to journalArticle

Dalpke, AH, Frey, M, Morath, S, Hartung, T & Heeg, K 2002, 'Interaction of lipoteichoic acid and CpG-DNA during activation of innate immune cells', Immunobiology, vol. 206, no. 4, pp. 392-407.
Dalpke, Alexander H. ; Frey, Markus ; Morath, Siegfried ; Hartung, Thomas ; Heeg, Klaus. / Interaction of lipoteichoic acid and CpG-DNA during activation of innate immune cells. In: Immunobiology. 2002 ; Vol. 206, No. 4. pp. 392-407.
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