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…
By N. W. Schröder, S. Morath, C. Alexander, L. Hamann, T. Hartung, U. Zähringer, U. Göbel, J. Weber, R. Schumann. Journal of Biological Chemistry, 2003
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Lipoteichoic acid (LTA) derived fromStreptococcus 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 PhastGelTM 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.
Subfields: Epidemiology, Immunology, Pharmacology
View Paper: https://www.semanticscholar.org/paper/3dcedbb91c20f05783de55bf3bdf8ba81292a040
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Citations in the corpus
- Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses (2009, background): “As is characteristic for gram-positive bacteria, TLR2 is activated by the cell wall components peptidoglycan and lipoteichoic acid (262, 327, 395).”
- Pattern recognition receptors in health and diseases (2021, background): “LTA, a TLR2 specific ligand, can significantly promote the secretion of tumor metastasis-related factors IL-6, TGF-β, and vascular endothelial growth factor (VEGF) in breast cancer cells,(355) thereby promoting the proliferation and metastatic invasion of breast cancer cells, and this promotion is r”
- Streptococcus Adherence and Colonization (2009, background): “LTA plays a part in streptococcal interactions with human tissue components (116, 239) and indeed triggers Toll-like receptor 2 (232, 532, 536), but the precise mechanism by which LTA might be involved in adherence is still not entirely clear.”