Pneumocystis pneumonia (PCP) is a fungal pulmonary disease with high mortality in immunocompromised patients. Neutrophils are essential in defending against fungal infections; however, their role in PCP is controversial. Here we aim to investigate the effects of neutrophil extracellular traps (NETs) on Pneumocystis clearance and lung injury using a mouse model of PCP. Intriguingly, although neutrophils play a fundamental role in defending against fungal infections, NETs failed to eliminate Pneumocystis, but instead impaired the killing of Pneumocystis. Mechanically, Pneumocystis triggered Leukotriene B4 (LTB4)-dependent neutrophil swarming, leading to agglutinative NET formation. Blocking Leukotriene B4 with its receptor antagonist Etalocib significantly reduced the accumulation and NET release of neutrophils in vitro and in vivo, enhanced the killing ability of neutrophils against Pneumocystis, and alleviated lung injury in PCP mice. This study identifies the deleterious role of agglutinative NETs in Pneumocystis infection and reveals a new way to prevent NET formation, which provides new insights into the pathogenesis of PCP.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/eji.202350779 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Circulating extracellular vesicles and neutrophil extracellular traps contribute to endothelial dysfunction in preeclampsia.
Front Immunol
December 2024
Barcelona Endothelium Team, Hospital Clínic de Barcelona, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Background: Preeclampsia (PE) is a pregnancy complication characterized by hypertension, proteinuria, endothelial dysfunction, and complement dysregulation. Placenta-derived extracellular vesicles (EVs), necessary in maternal-fetal communication, might contribute to PE pathogenesis. Moreover, neutrophil extracellular traps (NETs) play a pathogenic role in other complement-mediated pathologies, and their contribution in PE remains unexplored.
View Article and Find Full Text PDFCell-to-cell and organ-to-organ crosstalk in the pathogenesis of alcohol-associated liver disease.
eGastroenterology
October 2024
Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Alcohol-associated liver disease (ALD) is a growing global health concern and its prevalence and severity are increasing steadily. While bacterial endotoxin translocation into the portal circulation is a well-established key factor, recent evidence highlights the critical role of sterile inflammation, triggered by diverse stimuli, in alcohol-induced liver injury. This review provides a comprehensive analysis of the complex interactions within the hepatic microenvironment in ALD.
View Article and Find Full Text PDFAttenuation of neutrophil adhesion and formation of neutrophil extracellular traps by pooled human immune globulins.
Front Pharmacol
December 2024
Department of Ophthalmology, Loyola University Chicago, Maywood, IL, United States.
Introduction: This study investigated the efficacy of pooled human immune globulins (Flebogamma DIF) to combat the formation of neutrophil extracellular traps (NETs) and NETosis, along with neutrophil adhesion to corneal epithelial cells in response to dry eye disease relevant stimuli.
Methods: Human neutrophils were isolated by bead-based immunomagnetic depletion of non-target cells from human whole blood. NETosis was induced using phorbol 12-myristate 13-acetate (PMA) or anti-citrullinated histone 4 R3 antibody (H4R3 ACPA).
Identification of neutrophil extracellular traps (NETs)-related molecular clusters in prostate cancer: Implications for predicting biochemical recurrence.
Int Immunopharmacol
December 2024
Department of Urology, Urology Research Institute, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China; Department of Urology, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou 350212, China; Fujian Key Laboratory of Precision Medicine for Cancer, the First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, China. Electronic address:
Objective: To identify neutrophil extracellular traps (NETs)-related molecular clusters and establish a novel gene signature for predicting biochemical recurrence in prostate cancer (PCa).
Methods: The transcriptome and clinicaldata of PCa sampleswere obtained from The TCGA and GEO databases. To identify NET-related molecular clusters, consensus clustering analyses were performed.
Neutrophil Extracellular Traps Induce Brain Edema Around Intracerebral Hematoma via ERK-Mediated Regulation of MMP9 and AQP4.
Transl Stroke Res
December 2024
Department of Neurosurgery, The Second Affiliated Hospital of Chongqing Medical University, 74 Linjiang Rd, Yuzhong, Chongqing, 400010, China.
Perihematomal edema (PHE) significantly aggravates secondary brain injury in patients with intracerebral hemorrhage (ICH), yet its detailed mechanisms remain elusive. Neutrophil extracellular traps (NETs) are known to exacerbate neurological deficits and worsen outcomes after stroke. This study explores the potential role of NETs in the pathogenesis of brain edema following ICH.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!