ArticlePLoS pathogens2018
Klebsiella pneumoniae infection of murine neutrophils impairs their efferocytic clearance by modulating cell death machinery.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 94 citations in OpenAlex.
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- Immune evasion of multidrug-resistant bacteria: insights from lung innate immune cells and targeted therapies.Frontiers in cellular and infection microbiology · 2026Review
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- Nogo-B impairs efferocytosis in monocyte-derived macrophages and exacerbates septic liver injury.JHEP reports : innovation in hepatology · 2025Article
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- Bacterial translocation to mesenteric lymph nodes fueling surgical site infections: evidence, technical challenges and future directions.Journal of translational medicine · 2025Review
- Evidence of hypervirulent carbapenem-resistant Klebsiella pneumoniae in cats with urinary affections and associated humans in Egypt.Scientific reports · 2025Article
- Insights into the roles of macrophages in Klebsiella pneumoniae infections: a comprehensive review.Cellular & molecular biology letters · 2025Review
- High-alcohol-producing Klebsiella pneumoniae aggravates lung injury by affecting neutrophils and the airway epithelium.Cell reports. Medicine · 2025Article
- Staphylococcus aureus vesicles impair cutaneous wound healing through p38 MAPK-MerTK cleavage-mediated inhibition of macrophage efferocytosis.Cell communication and signaling : CCS · 2025Article
- Review
- Caspase-11 and NLRP3 exacerbate systemic Klebsiella infection through reducing mitochondrial ROS production.Frontiers in immunology · 2025Article
- Characterization of carbapenem-resistantFrontiers in cellular and infection microbiology · 2025Article
- The relationship between immune cell infiltration and necroptosis gene expression in sepsis: an analysis using single-cell transcriptomic data.Frontiers in cellular and infection microbiology · 2025Article
- Neutrophil diversity and function in health and disease.Signal transduction and targeted therapy · 2024Review
- Arthrospira maxima and biosynthesized zinc oxide nanoparticles as antibacterials against carbapenem-resistant Klebsiella pneumoniae and Acinetobacter baumannii: a review article.Microbial cell factories · 2024Review
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Neutrophils are the first infiltrating cell type essential for combating pneumoseptic infections by bacterial pathogens including Klebsiella pneumoniae (KPn). Following an infection or injury, removal of apoptotic infiltrates via a highly regulated process called efferocytosis is required for restoration of homeostasis, but little is known regarding the effect of bacterial infection on this process. Here we demonstrate that KPn infection impedes the efferocytic uptake of neutrophils in-vitro and in-vivo in lungs by macrophages. This impaired efferocytosis of infected neutrophils coincides with drastic reduction in the neutrophil surface exposure of apoptosis signature phospholipid phosphatidyserine (PS); and increased activity of phospholipid transporter flippases, which maintain PS in the inner leaflet of plasma membrane. Concomitantly, pharmacological inhibition of flippase activity enhanced PS externalization and restored the efferocytosis of KPn infected neutrophils. We further show that KPn infection interferes with apoptosis activation and instead activates non-apoptotic programmed cell death via activation of necroptosis machinery in neutrophils. Accordingly, pharmacological inhibition of necroptosis by RIPK1 and RIPK3 inhibitors restored the efferocytic uptake of KPn infected neutrophils in-vitro. Importantly, treatment of KPn infected mice with necroptosis inhibitor improved the disease outcome in-vivo in preclinical mouse model of KPn pneumonia. To our knowledge, this is the first report of neutrophil efferocytosis impairment by KPn via modulation of cell death pathway, which may provide novel targets for therapeutic intervention of this infection.
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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.