ArticleThe Journal of biological chemistry2015
Activation of Human Toll-like Receptor 4 (TLR4)·Myeloid Differentiation Factor 2 (MD-2) by Hypoacylated Lipopolysaccharide from a Clinical Isolate of Burkholderia cenocepacia.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 61 citations in OpenAlex.
- Review
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- The hidden language of gut-derived lipopolysaccharides: fine chemistry, huge immunological consequences.Chemical science · 2026Review
- Integrative in vitro and in silico evaluation of HSP60-derived peptides as immunomodulators of the TLR4/MD-2 complex.Scientific reports · 2025Article
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- TLR4 Targeting: A Promising Therapeutic Approach Across Multiple Human Diseases.Current protein & peptide science · 2025Review
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- Exploring the Mechanisms Underlying Cellular Uptake and Activation of Dendritic Cells by the GK-1 Peptide.ACS omega · 2024Article
- Comparative Cardioprotective Effectiveness: NOACs vs. Nattokinase-Bridging Basic Research to Clinical Findings.Biomolecules · 2024Review
- Monophosphoryl lipid A as a co-adjuvant in methicillin-resistant Staphylococcus aureus vaccine development: improvement of immune responses in a mouse model of infection.Immunologic research · 2024Article
- Polymyxin Resistance and Heteroresistance Are Common in Clinical Isolates ofMicrobiology spectrum · 2023Article
- The chemistry of gut microbiome-derived lipopolysaccharides impacts on the occurrence of food allergy in the pediatric age.Frontiers in molecular biosciences · 2023Article
- Human Cryptic Host Defence Peptide GVF27 Exhibits Anti-Infective Properties against Biofilm Forming Members of thePharmaceuticals (Basel, Switzerland) · 2022Article
- HSP60-Derived Peptide as an LPS/TLR4 Modulator: AnFrontiers in cardiovascular medicine · 2022Article
- Full-Atom Model of the Agonist LPS-Bound Toll-like Receptor 4 Dimer in a Membrane Environment.Chemistry (Weinheim an der Bergstrasse, Germany) · 2021Article
- Structure of the O-Antigen and the Lipid A from the Lipopolysaccharide of Fusobacterium nucleatum ATCC 51191.Chembiochem : a European journal of chemical biology · 2021Article
- A chronic strain of the cystic fibrosis pathogen Pandoraea pulmonicola expresses a heterogenous hypo-acylated lipid A.Glycoconjugate journal · 2021Article
- Tailored Modulation of Cellular Pro-inflammatory Responses With Disaccharide Lipid A Mimetics.Frontiers in immunology · 2021Article
- Insight Into Polysaccharides FromFrontiers in immunology · 2021Article
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Authors and funding
15 authors at 9 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lung infection by Burkholderia species, in particular Burkholderia cenocepacia, accelerates tissue damage and increases post-lung transplant mortality in cystic fibrosis patients. Host-microbe interplay largely depends on interactions between pathogen-specific molecules and innate immune receptors such as Toll-like receptor 4 (TLR4), which recognizes the lipid A moiety of the bacterial lipopolysaccharide (LPS). The human TLR4·myeloid differentiation factor 2 (MD-2) LPS receptor complex is strongly activated by hexa-acylated lipid A and poorly activated by underacylated lipid A. Here, we report that B. cenocepacia LPS strongly activates human TLR4·MD-2 despite its lipid A having only five acyl chains. Furthermore, we show that aminoarabinose residues in lipid A contribute to TLR4-lipid A interactions, and experiments in a mouse model of LPS-induced endotoxic shock confirmed the proinflammatory potential of B. cenocepacia penta-acylated lipid A. Molecular modeling combined with mutagenesis of TLR4-MD-2 interactive surfaces suggests that longer acyl chains and the aminoarabinose residues in the B. cenocepacia lipid A allow exposure of the fifth acyl chain on the surface of MD-2 enabling interactions with TLR4 and its dimerization. Our results provide a molecular model for activation of the human TLR4·MD-2 complex by penta-acylated lipid A explaining the ability of hypoacylated B. cenocepacia LPS to promote proinflammatory responses associated with the severe pathogenicity of this opportunistic bacterium.
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