ArticleJournal of immunology (Baltimore, Md. : 1950)2013
Leukotriene B4 enhances innate immune defense against the puerperal sepsis agent Streptococcus pyogenes.
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. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 53 citations in OpenAlex.
- Potential role of extracellular vesicles in bacterial phagocytosis during Escherichia coli pneumonia in ex vivo perfused human lungs.Intensive care medicine experimental · 2026Article
- Arachidonic acid metabolism in health and disease.MedComm · 2023Review
- Leukotrienes in Innate Immunity: Still Underappreciated after All These Years?Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- Toxoplasma gondii Infection Decreases Intestinal 5-Lipoxygenase Expression, while Exogenous LTBInfection and immunity · 2022Article
- Integrated ONT Full-Length Transcriptome and Metabolism Reveal the Mechanism Affecting Ovulation in Muscovy Duck (Frontiers in veterinary science · 2022Article
- Melanin Produced bymSphere · 2021Article
- Genome-Wide Screens Identify Group A Streptococcus Surface Proteins Promoting Female Genital Tract Colonization and Virulence.The American journal of pathology · 2020Article
- Article
- Mesenchymal Stem Cell-Derived Extracellular Vesicles Decrease Lung Injury in Mice.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Protein kinase D mediates inflammatory responses of human placental macrophages to Group B Streptococcus.American journal of reproductive immunology (New York, N.Y. : 1989) · 2019Article
- Excessive localized leukotriene B4 levels dictate poor skin host defense in diabetic mice.JCI insight · 2018Article
- Macrophage-derived LTB4 promotes abscess formation and clearance of Staphylococcus aureus skin infection in mice.PLoS pathogens · 2018Article
- Prostaglandins DJournal of lipid research · 2018Article
- Variation in Macrophage Phagocytosis ofPathogens & immunity · 2018Article
- Leukotriene BScientific reports · 2017Article
- Too much of a good thing: How modulating LTBSeminars in immunology · 2017Review
- The STAT4/MLL1 Epigenetic Axis Regulates the Antimicrobial Functions of Murine Macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Differing mechanisms of surviving phagosomal stress among group B Streptococcus strains of varying genotypes.Virulence · 2017Article
- Pharmacological Targeting of the Host-Pathogen Interaction: Alternatives to Classical Antibiotics to Combat Drug-Resistant Superbugs.Trends in pharmacological sciences · 2017Review
- Biochemical and immunological characterization of a novel monoclonal antibody against mouse leukotriene B4 receptor 1.PloS one · 2017Article
Corrections and comments
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Authors and funding
6 authors at 5 institutions in 2 countries.
Funding
Abstract
Puerperal sepsis is a leading cause of maternal mortality worldwide. Streptococcus pyogenes [group A Streptococcus; (GAS)] is a major etiologic agent of severe postpartum sepsis, yet little is known regarding the pathogenesis of these infections. Tissue macrophages provide innate defense against GAS, and their actions are highly regulated. The intracellular second messenger cAMP can negatively regulate macrophage actions against GAS. Because leukotriene (LT) B(4) has been shown to suppress intracellular cAMP in macrophages, we hypothesized that it could enhance innate defenses against GAS. We assessed the capacity of LTB(4) to modulate antistreptococcal actions of human macrophages, including placental and decidual macrophages and used a novel intrauterine infection model of GAS in mice lacking the 5-lipoxygenase enzyme to determine the role of endogenous LTs in host defense against this pathogen. Animals lacking 5-lipoxygenase were significantly more vulnerable to intrauterine GAS infection than were wild-type mice and showed enhanced dissemination of bacteria out of the uterus and a more robust inflammatory response than did wild-type mice. In addition, LTB(4) reduced intracellular cAMP levels via the BLT1 receptor and was a potent stimulant of macrophage phagocytosis and NADPH oxidase-dependent intracellular killing of GAS. Importantly, interference was observed between the macrophage immunomodulatory actions of LTB(4) and the cAMP-inducing lipid PGE(2), suggesting that interplay between pro- and anti-inflammatory compounds may be important in vivo. This work underscores the potential for pharmacological targeting of lipid mediator signaling cascades in the treatment of invasive GAS infections.
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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.