Peptidoglycan- and Lipoteichoic Acid-induced Cell Activation Is Mediated by Toll-like Receptor 2
Open accessAbstract
The life-threatening complications of sepsis in humans are elicited by infection with Gram-negative as well as Gram-positive bacteria. Recently, lipopolysaccharide (LPS), a major biologically active agent of Gram-negative bacteria, was shown to mediate cellular activation by a member of the human Toll-like receptor family, Toll-like receptor (TLR) 2. Here we investigate the mechanism of cellular activation by soluble peptidoglycan (sPGN) and lipoteichoic acid (LTA), main stimulatory components of Gram-positive bacteria. Like LPS, sPGN and LTA bind to the glycosylphosphatidylinositol-anchored membrane protein CD14 and induce activation of the transcription factor NF-kappaB in host cells like macrophages. We show that whole Gram-positive bacteria, sPGN and LTA induce the activation of NF-kappaB in HEK293 cells expressing TLR2 but not in cells expressing TLR1 or TLR4. The sPGN- and LTA-induced NF-kappaB activation was not inhibited by polymyxin B, an antibiotic that binds and neutralizes LPS. Coexpression together with membrane CD14 enhances sPGN signal transmission through TLR2. In contrast to LPS signaling, activation of TLR2 by sPGN and LTA does not require serum. These findings identify TLR2 as a signal transducer for sPGN and LTA in addition to LPS.
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Δiag mutant lacks ability to properly anchor LTA.
“We have previously described a GBS mutant (Δiag) that lacks the ability to properly anchor (LTA) (6), a known TLR2 ligand (30).”
From Bacterial induction of Snail1 contributes to blood-brain barrier disruption (2015) · cites this paper as [30]
LTA is a known TLR2 ligand.
“a known TLR2 ligand (30).”
From Bacterial induction of Snail1 contributes to blood-brain barrier disruption (2015) · cites this paper as [30]
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- Authors
- Schwandner, R., Dziarski, R., Wesche, H., Rothe, M., & Kirschning, C. J.
- Affiliations
- Indiana University School of Medicine (US)
- Corresponding author
- Kirschning, Carsten J.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1999-06
- Volume
- 274
- Issue
- 25
- Pages
- 17406-17409
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2008152503
- Cited by
- 1,704
- References
- 39
- Citations by year
- 2026: 21 · 2025: 14 · 2024: 20 · 2023: 25 · 2022: 31 · 2021: 45 · 2020: 21 · 2019: 43 · 2018: 39 · 2017: 40 · 2016: 51 · 2015: 26 · 2014: 51 · 2013: 74 · 2012: 59
- FWCI
- 33.87
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Allergy and Infectious Diseases (AI-28797, R01AI028797)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Health Sciences › Medicine › Infectious Diseases › Tuberculosis Research and Epidemiology
- Keywords
- TLR2, peptidoglycan, lipoteichoic acid, Gram-positive bacteria, CD14, NF-κB activation, macrophage activation, sepsis, lipopolysaccharide, polymyxin B, TLR1, TLR4, bacterial cell wall recognition
- MeSH terms
- Cell Line, Gram-Negative Bacteria, Gram-Positive Bacteria, Humans, Lipopolysaccharides, Membrane Glycoproteins, Peptidoglycan, Polymyxin B, Receptors, Cell Surface, Teichoic Acids, Signal Transduction, Transcriptional Activation, NF-kappa B, Glycosylphosphatidylinositols, Lipopolysaccharide Receptors, Drosophila Proteins, Toll-Like Receptors, Toll-Like Receptor 1, Toll-Like Receptor 2, Toll-Like Receptor 4
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