ArticleJCI insight2020
C5a impairs phagosomal maturation in the neutrophil through phosphoproteomic remodeling.
Article in JCI insight, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Genome-Scale Meta-analysis of Host Responses to Staphylococcus aureus Identifies Pathways for Host-Directed Therapeutic Targeting.The Journal of infectious diseases · 2025Pooled it
- Altered Degranulation and pH of Neutrophil Phagosomes Impacts Antimicrobial Efficiency in Cystic Fibrosis.Frontiers in immunology · 2020Trial
- Functional immune changes are conserved in COVID-19 and trauma patients receiving intensive care.Nature communications · 2026Article
- Colchicine as an Adjunctive Therapy to Improve Ischemic Stroke Reperfusion Outcomes in Mice.CNS neuroscience & therapeutics · 2026Article
- TOM1 family proteins: from cargo sorting to immune dysregulation and cancer.Cell communication and signaling : CCS · 2026Review
- Balancing inflammation and regeneration: immune cell dynamics in nerve repair: a comprehensive review.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- A subset of neutrophil phagosomes is characterised by pulses of Class I PI3K activity.Disease models & mechanisms · 2025Article
- Immunosenescence in Sepsis: Molecular Mechanisms and Potential Therapeutic Targets.Aging and disease · 2025Review
- The complement system: A key player in the host response to infections.European journal of immunology · 2024Review
- The formation and function of the neutrophil phagosome.Immunological reviews · 2023Review
- Article
- Sepsis-induced immunosuppression: mechanisms, diagnosis and current treatment options.Military Medical Research · 2022Review
- Real-time visualization of phagosomal pH manipulation byFrontiers in cellular and infection microbiology · 2022Article
- miRNA Involvement in Cerebral Ischemia-Reperfusion Injury.Frontiers in neuroscience · 2022Review
- Immune modulation after traumatic brain injury.Frontiers in medicine · 2022Review
- The C5a/C5aR1 Axis Contributes to the Pathogenesis of Acute Cystitis Through Enhancement of Adhesion and Colonization of UropathogenicFrontiers in cellular and infection microbiology · 2022Article
- Neutrophil kinetics and function after major trauma: A systematic review.World journal of critical care medicine · 2021Article
- Role of Notch in endothelial biology.Angiogenesis · 2021Review
- Proteomic, biomechanical and functional analyses define neutrophil heterogeneity in systemic lupus erythematosus.Annals of the rheumatic diseases · 2021Article
- Ventilator-associated pneumonia in critically ill patients with COVID-19.Critical care (London, England) · 2021Observational
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
Critical illness is accompanied by the release of large amounts of the anaphylotoxin, C5a. C5a suppresses antimicrobial functions of neutrophils which is associated with adverse outcomes. The signaling pathways that mediate C5a-induced neutrophil dysfunction are incompletely understood. Healthy donor neutrophils exposed to purified C5a demonstrated a prolonged defect (7 hours) in phagocytosis of Staphylococcus aureus. Phosphoproteomic profiling of 2712 phosphoproteins identified persistent C5a signaling and selective impairment of phagosomal protein phosphorylation on exposure to S. aureus. Notable proteins included early endosomal marker ZFYVE16 and V-ATPase proton channel component ATPV1G1. An assay of phagosomal acidification demonstrated C5a-induced impairment of phagosomal acidification, which was recapitulated in neutrophils from critically ill patients. Examination of the C5a-impaired protein phosphorylation indicated a role for the PI3K VPS34 in phagosomal maturation. Inhibition of VPS34 impaired neutrophil phagosomal acidification and killing of S. aureus. This study provides a phosphoproteomic assessment of human neutrophil signaling in response to S. aureus and its disruption by C5a, identifying a defect in phagosomal maturation and mechanisms of immune failure in critical illness.
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What OpenQuestion holds
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.