ArticleCritical care (London, England)2019
Flagellin attenuates experimental sepsis in a macrophage-dependent manner.
Article in Critical care (London, England), 2019. 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, 28 citations in OpenAlex.
- Multiomics Profiling Identifies Blood-Based Diagnostic Markers for Sepsis.Journal of cellular physiology · 2026Article
- Estrogen receptor β deficiency increases susceptibility to sepsis through metabolic reprogramming-induced macrophage pyroptosis.The Journal of clinical investigation · 2026Article
- Toll-like receptor 5 on monocyte as a biomarker of mortality risk in patients with sepsis.BMC infectious diseases · 2026Article
- Immunomodulatory Nanozymes Eradicate Intracellular Infections and Rescue Immunoparalysis for Treating Multidrug-Resistant Bacterial Sepsis.Exploration (Beijing, China) · 2025Article
- Exogenous prostaglandin DFrontiers in veterinary science · 2025Article
- Investigating the role of the mPGES-PGE₂-EP4 pathway inFrontiers in veterinary science · 2025Article
- Probiotic bacteria-released extracellular vesicles enhance macrophage phagocytosis in polymicrobial sepsis by activating the FPR1/2 pathway.Molecular medicine (Cambridge, Mass.) · 2024Article
- Toll-like receptors in health and disease.MedComm · 2024Review
- PAMPs and DAMPs in Sepsis: A Review of Their Molecular Features and Potential Clinical Implications.International journal of molecular sciences · 2024Review
- Regulation of toll-like receptor (TLR) signaling pathways in atherosclerosis: from mechanisms to targeted therapeutics.Acta pharmacologica Sinica · 2023Review
- Mesenchymal stromal cells and alpha-1 antitrypsin have a strong synergy in modulating inflammation and its resolution.Theranostics · 2023Article
- Progranulin aggravates lethal Candida albicans sepsis by regulating inflammatory response and antifungal immunity.PLoS pathogens · 2022Article
- Syringaresinol Resisted Sepsis-Induced Acute Lung Injury by Suppressing Pyroptosis Via the Oestrogen Receptor-β Signalling Pathway.Inflammation · 2022Article
- Identification of hub genes for adult patients with sepsis via RNA sequencing.Scientific reports · 2022Article
- Gut microbiota-derived indole 3-propionic acid partially activates aryl hydrocarbon receptor to promote macrophage phagocytosis and attenuate septic injury.Frontiers in cellular and infection microbiology · 2022Article
- Pattern recognition receptors as therapeutic targets for bacterial, viral and fungal sepsis.International immunopharmacology · 2021Review
- TLR7 Expression Aggravates Invasive Pulmonary Aspergillosis by Suppressing Anti-Infection and immunity · 2021Article
- Neutrophil-derived trail is a proinflammatory subtype of neutrophil-derived extracellular vesicles.Theranostics · 2021Article
- Article
- Interleukin-26 is overexpressed in human sepsis and contributes to inflammation, organ injury, and mortality in murine sepsis.Critical care (London, England) · 2019Article
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundSepsis is the leading cause of death among critically ill patients, and no specific therapeutic agent is currently approved for the treatment of sepsis.
methodsWe assessed the effects of flagellin administration on survival, bacterial burden, and tissue injury after sepsis. In addition, we examined the effects on phagocytosis and bacterial killing in monocytes/macrophages.
resultsTherapeutic administration of flagellin increased bacterial clearance, decreased organ inflammation and injury, and reduced immune cell apoptosis after experimental sepsis, in a Toll-like receptor 5 (TLR5)-dependent manner. Macrophages, but not neutrophils, mediated the beneficial effects of flagellin on experimental sepsis, and flagellin induced macrophage polarization into M1 in septic mice. Flagellin treatment could directly enhance phagocytosis and bacterial killing of macrophages, but not neutrophils. Subsequent studies demonstrated that flagellin could promote phagosome formation and increase reactive oxygen species (ROS) levels in macrophages. Finally, we found that the expression of TLR5 was significantly elevated on the surface of circulating monocytes, but not neutrophils, from patients with sepsis. Higher expression levels of TLR5 on monocytes were associated with increased mortality, documented bacteremia, and higher Sequential Organ Failure Assessment scores of the septic patients. Moreover, flagellin treatment rescued the impaired phagocytosis and bacterial killing ability of monocytes/macrophages from patients who died of sepsis.
conclusionsThese novel findings not only established the potential value of application of flagellin as an immunoadjuvant in treating sepsis, but also provided new insights into targeted therapeutic strategy on the basis of monocyte TLR5 expression in septic patients.
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