ArticlePloS one2012
Pathways involved in the synergistic activation of macrophages by lipoteichoic acid and hemoglobin.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Fibrin-rich environment drives catheter-associated UTIs by suppressing macrophage defenses.Nature communications · 2026Article
- Hemoglobin inhibits fibroblast-to-cardiomyocyte reprogramming via TLR2/TLR4-dependent chromatin compaction.Molecular therapy. Nucleic acids · 2026Article
- Cell-free hemoglobin triggers macrophage cytokine production via TLR4 and MyD88.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- CCL20/CCR6 Mediated Macrophage Activation and Polarization Can Promote Adenoid Epithelial Inflammation in Adenoid Hypertrophy.Journal of inflammation research · 2022Article
- Inflammatory hydrocephalus.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2021Article
- Article
- Inflammation in acquired hydrocephalus: pathogenic mechanisms and therapeutic targets.Nature reviews. Neurology · 2020Review
- Inflammatory Response to Different Toxins in Experimental Sepsis Models.International journal of molecular sciences · 2019Review
- TLR4 genetic variation is associated with inflammatory responses in Gram-positive sepsis.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2017Article
- Inducible nitric oxide synthase (NOS-2) in subarachnoid hemorrhage: Regulatory mechanisms and therapeutic implications.Brain circulation · 2016Article
- Methemoglobin is an endogenous toll-like receptor 4 ligand-relevance to subarachnoid hemorrhage.International journal of molecular sciences · 2015Article
- HMGB1 Binds to Lipoteichoic Acid and Enhances TNF-α and IL-6 Production through HMGB1-Mediated Transfer of Lipoteichoic Acid to CD14 and TLR2.Journal of innate immunity · 2015Article
- Inhibitory effects of simvastatin on staphylococcus aureus lipoteichoic acid-induced inflammation in human alveolar macrophages.Clinical and experimental medicine · 2014Article
- Hemoglobin expression in nonerythroid cells: novel or ubiquitous?International journal of inflammation · 2014Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Lipoteichoic acid (LTA) is a Gram-positive cell surface molecule that is found in both a cell-bound form and cell-free form in the host during an infection. Hemoglobin (Hb) can synergize with LTA, a TLR2 ligand, to potently activate macrophage innate immune responses in a TLR2- and TLR4-dependent way. At low levels of LTA, the presence of Hb can result in a 200-fold increase in the secretion of IL-6 following macrophage activation. Six hours after activation, the macrophage genes that are most highly up-regulated by LTA plus Hb activation compared to LTA alone are cytokines, chemokines, receptors and interferon-regulated genes. Several of these genes exhibit a unique TLR4-dependent increase in mRNA levels that continued to rise more than eight hours after stimulation. This prolonged increase in mRNA levels could be the result of an extended period of NF-κB nuclear localization and the concurrent absence of the NF-κB inhibitor, IκBα, after stimulation with LTA plus Hb. Dynasore inhibition experiments indicate that an endocytosis-dependent pathway is required for the TLR4-dependent up-regulation of IL-6 secretion following activation with LTA plus Hb. In addition, interferon-β mRNA is present after activation with LTA plus Hb, suggesting that the TRIF/TRAM-dependent pathway may be involved. Hb alone can elicit the TLR4-dependent secretion of TNF-α from macrophages, so it may be the TLR4 ligand. Hb also led to secretion of high mobility group box 1 protein (HMGB1), which synergized with LTA to increase secretion of IL-6. The activation of both the TLR2 and TLR4 pathways by LTA plus Hb leads to an enhanced innate immune response.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.