ArticleFrontiers in immunology2022
Neonatal NET-Inhibitory Factor improves survival in the cecal ligation and puncture model of polymicrobial sepsis by inhibiting neutrophil extracellular traps.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 10 citations in OpenAlex.
- Neutrophil extracellular traps offer a new therapeutic target for elephant endotheliotropic herpes virus-hemorrhagic disease (EEHV-HD).Communications biology · 2026Article
- Neutrophil extracellular traps and microglia/macrophages interactions in stroke: from thromboinflammation to immunotherapy.Frontiers in immunology · 2026Review
- Protein Fragments: From Biomarkers to Therapeutic Targets-A Focus on α1-Antitrypsin-Derived Peptides.Mediators of inflammation · 2026Review
- NETosis inhibitory activity of LBW newborns' cord blood plasma reverses lupus-associated immunopathology.Frontiers in immunology · 2026Article
- NETosis-specific cell death: a novel mechanism in the pathogenesis of gouty arthritis.European journal of medical research · 2025Review
- Antimicrobial and Immunomodulatory Effects of Punicalagin and Meropenem in a Murine Model of Sublethal Sepsis.Antibiotics (Basel, Switzerland) · 2025Article
- The COVID-19 thrombus: distinguishing pathological, mechanistic, and phenotypic features and management.Journal of thrombosis and thrombolysis · 2025Review
- Gut microbiota dysbiosis aggravates sepsis-induced lung injury by promoting neutrophil extracellular traps and suppressing host integrin defense.Frontiers in microbiology · 2025Article
- Neonatal NET-inhibitory factor inhibits macrophage extracellular trap formation.Blood advances · 2024Article
- The Neonatal Immune System and Respiratory Pathogens.Microorganisms · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
Abstract
Introduction: Neutrophil extracellular traps (NETs) clear pathogens but may contribute Q8 pathogenically to host inflammatory tissue damage during sepsis. Innovative therapeutic agents targeting NET formation and their potentially harmful collateral effects remain understudied. Methods: We investigated a novel therapeutic agent, neonatal NET-Inhibitory Factor (nNIF), in a mouse model of experimental sepsis - cecal ligation and puncture (CLP). We administered 2 doses of nNIF (1 mg/ kg) or its scrambled peptide control intravenously 4 and 10 hours after CLP treatment and assessed survival, peritoneal fluid and plasma NET formation using the MPO-DNA ELISA, aerobic bacterial colony forming units (CFU) using serial dilution and culture, peritoneal fluid and stool microbiomes using 16S rRNA gene sequencing, and inflammatory cytokine levels using a multiplexed cytokine array. Meropenem (25 mg/kg) treatment served as a clinically relevant treatment for infection. Results: We observed increased 6-day survival rates in nNIF (73%) and meropenem (80%) treated mice compared to controls (0%). nNIF decreased NET formation compared to controls, while meropenem did not impact NET formation. nNIF treatment led to increased peritoneal fluid and plasma bacterial CFUs consistent with loss of NET-mediated extracellular microbial killing, while nNIF treatment alone did not alter the peritoneal fluid and stool microbiomes compared to vehicle-treated CLP mice. nNIF treatment also decreased peritoneal TNF-a inflammatory cytokine levels compared to scrambled peptide control. Furthermore, adjunctive nNIF increased survival in a model of sub-optimal meropenem treatment (90% v 40%) in CLP-treated mice. Discussion: Thus, our data demonstrate that nNIF inhibits NET formation in a translationally relevant mouse model of sepsis, improves survival when given as monotherapy or as an adjuvant with antibiotics, and may play an important protective role in sepsis.
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