ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Impaired TLR5 functionality is associated with survival in melioidosis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02217592 (Causes and Factors Associated With Outcomes in Community-acquired Sepsis and Severe Sepsis in Northeast), which is not on this map. Cited by 33 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Causes and Factors Associated With Outcomes in Community-acquired Sepsis and Severe Sepsis in Northeast (NE) Thailand
Who cites it
33 citing papers in PubMed, 45 citations in OpenAlex.
- A first-in-human study of KMRC011, a potential treatment for acute radiation syndrome, to explore tolerability, pharmacokinetics, and pharmacodynamics.Clinical and translational science · 2021Trial
- Targeting inflammasome, IL-1β, and coagulation in melioidosis.Frontiers in microbiology · 2026Review
- Polymorphic pseudogenes in the human genome - a comprehensive assessment.Human genetics · 2024Article
- Lack of Association of TLR1 and TLR5 Coding Variants with Mortality in a Large Multicenter Cohort of Melioidosis Patients.The American journal of tropical medicine and hygiene · 2024Article
- Burkholderia pseudomallei and melioidosis.Nature reviews. Microbiology · 2024Review
- Effects of Bacille Calmette Guerin (BCG) vaccination during COVID-19 infection.Computers in biology and medicine · 2021Article
- Activation of Toll-Like Receptors by Live Gram-Negative Bacterial Pathogens Reveals Mitigation of TLR4 Responses and Activation of TLR5 by Flagella.Frontiers in cellular and infection microbiology · 2021Article
- Lactoferrin is a dynamic protein in human melioidosis and is a TLR4-dependent driver of TNF-α release in Burkholderia thailandensis infection in vitro.PLoS neglected tropical diseases · 2020Article
- 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
- Article
- Human Melioidosis.Clinical microbiology reviews · 2020Review
- Article
- An Evolutionary Arms Race BetweenFrontiers in microbiology · 2020Review
- Role of Toll-Like Receptor 5 (TLR5) in Experimental Melioidosis.Infection and immunity · 2019Article
- Bacterial flagellin promotes viral entry via an NF-kB and Toll Like Receptor 5 dependent pathway.Scientific reports · 2019Article
- Flagellin-independent effects of a Toll-like receptor 5 polymorphism in the inflammatory response to Burkholderia pseudomallei.PLoS neglected tropical diseases · 2019Article
- Exonic sequencing identifies TLR1 genetic variation associated with mortality in Thais with melioidosis.Emerging microbes & infections · 2019Article
- Inflammasomes, Autophagy, and Cell Death: The Trinity of Innate Host Defense against Intracellular Bacteria.Mediators of inflammation · 2019Review
- Article
- A nonsense mutation in TLR5 is associated with survival and reduced IL-10 and TNF-α levels in human melioidosis.PLoS neglected tropical diseases · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Melioidosis is infection caused by the flagellated saprophyte Burkholderia pseudomallei. TLR5 is a pathogen recognition receptor activated by bacterial flagellin. We studied a genetic variant that encodes a defective TLR5 protein, TLR5(1174C)>T, to elucidate the role of TLR5 in melioidosis. We measured NF-κB activation induced by B. pseudomallei in human embryonic kidney-293 cells transfected with TLR5 and found that B. pseudomallei induced TLR5(1174C)- but not TLR5(1174T)-dependent activation of NF-κB. We tested the association of TLR5(1174C)>T with outcome in 600 Thai subjects with melioidosis. In a dominant model, TLR5(1174C)>T was associated with protection against in-hospital death (adjusted odds ratio: 0.20; 95% confidence interval: 0.08-0.50; p = 0.001) and organ failure (adjusted odds ratio: 0.37; 95% confidence interval: 0.19-0.71; p = 0.003). We analyzed blood cytokine production induced by flagellin or heat-killed B. pseudomallei by TLR5(1174C)>T genotype in healthy subjects. Flagellin induced lower monocyte-normalized levels of IL-6, IL-8, TNF-α, IL-10, MCP-1, IL-1ra, G-CSF, and IL-1β in carriers of TLR5(1174T) compared with carriers of TLR5(1174C). B. pseudomallei induced lower monocyte-normalized levels of IL-10 in carriers of TLR5(1174T). We conclude that the hypofunctional genetic variant TLR5(1174C)>T is associated with reduced organ failure and improved survival in melioidosis. This conclusion suggests a deleterious immunoregulatory effect of TLR5 that may be mediated by IL-10 and identifies this receptor as a potential therapeutic target in melioidosis.
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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.