ArticleThe Journal of clinical investigation2019
Staphylococcus aureus drives expansion of low-density neutrophils in diabetic mice.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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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.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Neutrophils and neutrophil extracellular traps in diabetes mellitus and its complications: Mechanisms and therapeutic implications.iScience · 2026Review
- NKG2A-mediated immune modulation of natural killer cells by Staphylococcus aureus.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Single-cell atlas of human gingiva unveils a NETs-related neutrophil subpopulation regulating periodontal immunity.Journal of advanced research · 2025Article
- Interaction of low-density neutrophils with other immune cells in the mechanism of inflammation.Molecular medicine (Cambridge, Mass.) · 2025Review
- Advances in Necrotizing Fasciitis Animal Models: Current Trends and Future Perspectives.Journal of inflammation research · 2025Review
- Gut Microbiota in Patients with Prediabetes.Nutrients · 2024Article
- Virulence characteristics of Gram-positive bacteria isolated from diabetic foot ulcers.FEMS microbes · 2024Article
- The effect of neutrophil extracellular traps in venous thrombosis.Thrombosis journal · 2023Review
- Enhanced Vulnerability of Diabetic Mice to HypervirulentPathogens (Basel, Switzerland) · 2023Article
- Novel mechanisms of thrombo-inflammation during infection: spotlight on neutrophil extracellular trap-mediated platelet activation.Research and practice in thrombosis and haemostasis · 2023Article
- Neutrophil heterogeneity and aging: implications for COVID-19 and wound healing.Frontiers in immunology · 2023Review
- Article
- Modulation of Gut Microbiota Metabolism in Obesity-Related Type 2 Diabetes Reduces Osteomyelitis Severity.Microbiology spectrum · 2022Article
- Neutrophils in chronic inflammatory diseases.Cellular & molecular immunology · 2022Review
- Molecular Prerequisites for Neutrophil Extracellular Trap Formation and Evasion Mechanisms ofFrontiers in immunology · 2022Review
- Exploring the Role of Low-Density Neutrophils DuringFrontiers in cellular and infection microbiology · 2022Review
- Tumor-Derived Factors Differentially Affect the Recruitment and Plasticity of Neutrophils.Cancers · 2021Article
- A specific low-density neutrophil population correlates with hypercoagulation and disease severity in hospitalized COVID-19 patients.JCI insight · 2021Article
- Adaptation ofToxins · 2021Article
- A Bittersweet Response to Infection in Diabetes; Targeting Neutrophils to Modify Inflammation and Improve Host Immunity.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 7 countries.
Funding
Abstract
Diabetic individuals are at considerable risk for invasive infection by Staphylococcus aureus, however, the mechanisms underlying this enhanced susceptibility to infection are unclear. We observed increased mortality following i.v. S. aureus infection in diabetic mice compared with nondiabetic controls, correlating with increased numbers of low-density neutrophils (LDNs) and neutrophil extracellular traps (NETs). LDNs have been implicated in the inflammatory pathology of diseases such as lupus, given their release of large amounts of NETs. Our goal was to describe what drives LDN increases during S. aureus infection in the diabetic host and mechanisms that promote increased NET production by LDNs. LDN development is dependent on TGF-β, which we found to be more activated in the diabetic host. Neutralization of TGF-β, or the TGF-β-activating integrin αvβ8, reduced LDN numbers and improved survival during S. aureus infection. Targeting S. aureus directly with MEDI4893*, an α toxin-neutralizing monoclonal antibody, blocked TGF-β activation, reduced LDNs and NETs, and significantly improved survival. A comparison of gene and protein expression in high-density neutrophils and LDNs identified increased GPCRs and elevated phosphatase and tensin homolog (PTEN) in the LDN subset. Inhibition of PTEN improved the survival of infected diabetic mice. Our data identify a population of neutrophils in infected diabetic mice that correlated with decreased survival and increased NET production and describe 3 therapeutic targets, a bacterial target and 2 host proteins, that prevented NET production and improved survival.
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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.