ArticleClinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases2017
TLR4 genetic variation is associated with inflammatory responses in Gram-positive sepsis.
Article in Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 36 citations in OpenAlex.
- "Just the Best Ones" combination: a new strategy for multi-epitope vaccine candidate based on immunoinformatics analysis to induce protective immunity against MRSA infection.Microbiology spectrum · 2026Article
- Circulating microRNAs and Plasma Gelsolin as Biomarkers of Sepsis: Molecular Insights and Prospects for Precision Medicine.Biomolecules · 2025Review
- Differential expression ofVeterinary world · 2025Article
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- Flagellin-modulated inflammasome pathways characterize the human alveolar macrophage response toInfection and immunity · 2024Article
- TLR4 sensing of IsdB ofmBio · 2024Article
- Next-generation humanized NSG-SGM3 mice are highly susceptible toFrontiers in immunology · 2023Article
- Study on the expression of TRIM7 in peripheral blood mononuclear cells of patients with sepsis and its early diagnostic value.BMC infectious diseases · 2022Article
- Toll-Like Receptor Signaling and Its Role in Cell-Mediated Immunity.Frontiers in immunology · 2022Review
- Low-dose mycophenolate mofetil improves survival in a murine model ofFrontiers in immunology · 2022Article
- Non-invasive sampling procedure revealing the molecular events at different abutments of bone-anchored hearing systems-A prospective clinical pilot study.Frontiers in neuroscience · 2022Article
- Antibiotic Combined with Epitope-Specific Monoclonal Antibody Cocktail Protects Mice Against Bacteremia and Acute Pneumonia from Methicillin-ResistantJournal of inflammation research · 2021Article
- Dissecting the Human Response toFrontiers in immunology · 2021Article
- Longitudinal profiling of plasma cytokines in melioidosis and their association with mortality: a prospective cohort study.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2020Article
- Diagnostic Value of miR-103 in Patients with Sepsis and Noninfectious SIRS and Its Regulatory Role in LPS-Induced Inflammatory Response by Targeting TLR4.International journal of genomics · 2020Article
- Development of a vaccine against Staphylococcus aureus invasive infections: Evidence based on human immunity, genetics and bacterial evasion mechanisms.FEMS microbiology reviews · 2020Review
- Predictive Validity of the qSOFA Score for Sepsis in Adults with Community-Onset Staphylococcal Infection in Thailand.Journal of clinical medicine · 2019Article
- Immunity toMicrobiology spectrum · 2019Review
- Acetic acid alleviates the inflammatory response and liver injury in septic mice by increasing the expression of TRIM40.Experimental and therapeutic medicine · 2019Article
- Association of TLR4 gene polymorphisms with childhood Henoch-Schönlein purpura in a Chinese population.Rheumatology international · 2017Article
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Authors and funding
21 authors at 7 institutions in 3 countries.
Funding
Abstract
objectivesTo identify important pathogen recognition receptor (PRR) pathways regulating innate immune responses and outcome in Staphylococcus aureus sepsis.
methodsWe analysed whether candidate PRR pathway genetic variants were associated with killed S. aureus-induced cytokine responses ex vivo and performed follow-up in vitro studies. We tested the association of our top-ranked variant with cytokine responses and clinical outcomes in a prospective multicentre cohort of patients with staphylococcal sepsis.
resultsAn intronic TLR4 polymorphism and expression quantitative trait locus, rs1927907, was highly associated with cytokine release induced by stimulation of blood from healthy Thai subjects with S. aureus ex vivo. S. aureus did not induce TLR4-dependent NF-κB activation in transfected HEK293 cells. In monocytes, tumor necrosis factor (TNF)-α release induced by S. aureus was not blunted by a TLR4/MD-2 neutralizing antibody, but in a monocyte cell line, TNF-α was reduced by knockdown of TLR4. In Thai patients with staphylococcal sepsis, rs1927907 was associated with higher interleukin (IL)-6 and IL-8 levels as well as with respiratory failure. S. aureus-induced responses in blood were most highly correlated with responses to Gram-negative stimulants whole blood.
conclusionsA genetic variant in TLR4 is associated with cytokine responses to S. aureus ex vivo and plasma cytokine levels and respiratory failure in staphylococcal sepsis. While S. aureus does not express lipopolysaccharide or activate TLR4 directly, the innate immune response to S. aureus does appear to be modulated by TLR4 and shares significant commonality with that induced by Gram-negative pathogens and lipopolysaccharide.
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