ArticleJournal of immunology (Baltimore, Md. : 1950)2008
Administration of a synthetic TLR4 agonist protects mice from pneumonic tularemia.
Article in Journal of immunology (Baltimore, Md. : 1950), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
38 citing papers in PubMed, 62 citations in OpenAlex.
- Development of Effective Medical Countermeasures Against the Main Biowarfare Agents: The Importance of Antibodies.Microorganisms · 2024Review
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- Boosting the IL-22 response using flagellin prevents bacterial infection in cigarette smoke-exposed mice.Clinical and experimental immunology · 2020Article
- TLR Agonists as Mediators of Trained Immunity: Mechanistic Insight and Immunotherapeutic Potential to Combat Infection.Frontiers in immunology · 2020Review
- Mechanisms of Epithelial Immunity Evasion by Respiratory Bacterial Pathogens.Frontiers in immunology · 2020Review
- Lung epithelial cells: therapeutically inducible effectors of antimicrobial defense.Mucosal immunology · 2018Review
- Funiculosin variants and phosphorylated derivatives promote innate immune responses via the Toll-like receptor 4/myeloid differentiation factor-2 complex.The Journal of biological chemistry · 2017Article
- Article
- Pharmacological Targeting of the Host-Pathogen Interaction: Alternatives to Classical Antibiotics to Combat Drug-Resistant Superbugs.Trends in pharmacological sciences · 2017Review
- Mitogen-activated protein kinases (MAPKs) are modulated during Francisella tularensis infection, but inhibition of extracellular-signal-regulated kinases (ERKs) is of limited therapeutic benefit.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2016Article
- A Toll-Like Receptor 5 Agonist Improves the Efficacy of Antibiotics in Treatment of Primary and Influenza Virus-Associated Pneumococcal Mouse Infections.Antimicrobial agents and chemotherapy · 2015Article
- TLR Agonists as Modulators of the Innate Immune Response and Their Potential as Agents Against Infectious Disease.Frontiers in immunology · 2014Review
- New therapeutic approaches for treatment of tularaemia: a review.Frontiers in cellular and infection microbiology · 2014Review
- Monocyte/macrophage inflammatory response pathways to combat Francisella infection: possible therapeutic targets?Frontiers in cellular and infection microbiology · 2014Review
- The immunobiology of toll-like receptor 4 agonists: from endotoxin tolerance to immunoadjuvants.Shock (Augusta, Ga.) · 2013Review
- The use of nanolipoprotein particles to enhance the immunostimulatory properties of innate immune agonists against lethal influenza challenge.Biomaterials · 2013Article
- Immunotherapy for tularemia.Virulence · 2013Review
- Structural Modifications of Bacterial Lipopolysaccharide that Facilitate Gram-Negative Bacteria Evasion of Host Innate Immunity.Frontiers in immunology · 2013Article
- Immunopharmacology of lipid A mimetics.Advances in pharmacology (San Diego, Calif.) · 2013Review
- Trial Watch: Experimental Toll-like receptor agonists for cancer therapy.Oncoimmunology · 2012Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Francisella tularensis is a Gram-negative intracellular pathogen that causes the zoonosis tularemia. Because F. tularensis LPS causes weak TLR4 activation, we hypothesized that administration of a synthetic TLR4 agonist, aminoalkyl glucosaminide phosphate (AGP), would boost the innate immune system and compensate for reduced TLR4 stimulation. Intranasal administration of AGPs induced intrapulmonary production of proinflammatory cytokines and chemokines. Mice treated with AGPs before and after inhalation of Francisella novicida exhibited augmented cytokine and inflammatory responses to infection; reduced bacterial replication in lung, liver, and spleen; and increased survival, whereas all PBS-treated control mice died within 4 days of infection, all AGP-treated mice showed prolonged time-to-death, and 30-60% of AGP-treated mice survived. The protective effect of AGP was lost in mice lacking IFN-gamma. Long-term survivors developed specific Th1 splenocyte responses and specific Abs dominated by IgG2 isotypes. Survivors were fully protected from rechallenge with aerosolized F. novicida. Thus, preventive administration of AGP successfully modulated innate immune responses to aerosolized F. novicida, leading to protective immunity to pneumonic tularemia. This is the first report of the protective effect of a TLR ligand on resistance to F. novicida-induced pneumonic tularemia.
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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.