Cited by 641Immune Response and InflammationTuberculosis Research and EpidemiologyT-cell and B-cell Immunology

Lipoteichoic Acid (LTA) of Streptococcus pneumoniaeand Staphylococcus aureus Activates Immune Cells via Toll-like Receptor (TLR)-2, Lipopolysaccharide-binding Protein (LBP), and CD14, whereas TLR-4 and MD-2 Are Not Involved

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Schröder, Nicolas W.J., Morath, Siegfried, Alexander, Christian, Hamann, Lutz, Hartung, Thomas, Zähringer, Ulrich, Göbel, Ulf B., Weber, Joerg R. +1 more·2003·Journal of Biological Chemistry

Abstract

Lipoteichoic acid (LTA) derived from Streptococcus pneumoniae, purified employing a chloroform/methanol protocol, and from Staphylococcus aureus, prepared by the recently described butanol extraction procedure, was investigated regarding its interaction with lipopolysaccharide (LPS)-binding protein (LBP), CD14, Toll-like receptors (TLRs)-2 and -4, and MD-2. LTA from both organisms induced cytokine synthesis in human mononuclear phagocytes. Activation was LBP- and CD14-dependent, and formation of complexes of LTA with LBP and soluble CD14 as well as catalytic transfer of LTA to CD14 by LBP was verified by PhastGel(TM) native gel electrophoresis. Human embryonic kidney (HEK) 293/CD14 cells and Chinese hamster ovary (CHO) cells were responsive to LTA only after transfection with TLR-2. Additional transfection with MD-2 did not affect stimulation of these cells by LTA. Our data suggest that innate immune recognition of LTA via LBP, CD14, and TLR-2 represents an important mechanism in the pathogenesis of systemic complications in the course of infectious diseases brought about by the clinically most important Gram-positive pathogens. However, the involvement of TLR-4 and MD-2 in this process was ruled out.

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  • Gram-positive bacteria may also contribute to cytokine stimulation; lipoteichoic acid causes cytokine induction in mononuclear phagocytes and synergises with peptidoglycan to result in higher cytokine levels.

    “However, Gram positive bacteria may also contribute to the stimulation in the production of cytokines. Lipoteichoic acid (LTA) represents a class of amphiphilic molecules anchored to the outer face of the cytoplasmic membrane in Gram positive bacteria that causes cytokine induction in mononuclear phagocytes and a synergism with peptidoglycan (PG) has been described resulting in higher cytokine lev”

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  1. Greenwood, B. (1999) Philos. Trans. R. Soc. Lond. B. Biol. Sci. 354, 777-785
  2. De Kimpe, S. J., Kengatharan, M., Thiemermann, C., and Vane, J. R. (1995) Proc. Natl. Acad. Sci. U. S. A. 92, 10359 -10363
  3. Holtje, J. V., and Tomasz, A. (1975) Proc. Natl. Acad. Sci. U. S. A. 72, 1690 -1694

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Authors
Schröder, N. W. J., Morath, S., Alexander, C., Hamann, L., Hartung, T., Zähringer, U., Göbel, U. B., Weber, J. R., & Schumann, R. R.
Affiliations
  • Humboldt-Universität zu Berlin (DE)
  • University of Konstanz (DE)
  • Research Center Borstel - Leibniz Lung Center (DE)
Corresponding author
Schumann, Ralf R.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2003-05
Volume
278
Issue
18
Pages
15587-15594
ISSN
0021-9258 (ISSN-L)
OpenAlex
W2079605309
Cited by
641
References
68
Citations by year
2026: 11 · 2025: 9 · 2024: 20 · 2023: 21 · 2022: 19 · 2021: 21 · 2020: 15 · 2019: 26 · 2018: 13 · 2017: 29 · 2016: 27 · 2015: 18 · 2014: 40 · 2013: 28 · 2012: 32
FWCI
11.46
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Deutsche Forschungsgemeinschaft
  • Bundesministerium für Bildung und Forschung
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
  • Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords
lipoteichoic acid, Streptococcus pneumoniae, Staphylococcus aureus, TLR2, lipopolysaccharide-binding protein, CD14, MD-2, TLR4, innate immune recognition, cytokine production, mononuclear phagocytes
MeSH terms
Lipopolysaccharide-Binding Protein, Acute-Phase Proteins, Animals, Antigens, Surface, Carrier Proteins, Cells, Cultured, Cricetinae, Humans, Lipopolysaccharides, Membrane Glycoproteins, Monocytes, Receptors, Cell Surface, Staphylococcus aureus, Streptococcus pneumoniae, Teichoic Acids, Tumor Necrosis Factor-alpha, CHO Cells, Lipopolysaccharide Receptors, Toll-Like Receptors, Toll-Like Receptor 2, Toll-Like Receptor 4, Lymphocyte Antigen 96

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