MACROPHAGES COORDINATE IMMUNE RESPONSE TO LASER-INDUCED INJURY VIA EXTRACELLULAR TRAPS DOI Open Access
Federica Maria Conedera, Despina Kokona, Martin S. Zinkernagel

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Oct. 17, 2023

ABSTRACT Macrophages/monocytes, the primary contributors to chronic inflammation in degenerated retinas, orchestrate intricate immune responses. They remain enigmatic their local coordination and activation mechanisms. Innovations experimental systems enable real-time exploration of cell interactions temporal dimensions response. In preclinical mouse models, we use vivo microscopy unravel how macrophages/monocytes govern microglia PL responses spatio-temporally. Our findings underscore pivotal role innate cells, especially macrophages/monocytes, regulating retinal repair. The absence neutrophil macrophage infiltration aids parenchymal integrity restoration, while depletion, particularly impedes vascular recovery. Innate when activated, release chromatin granular proteins, forming extracellular traps (ETs), critical for tissue repair by modulating T-cell investigations demonstrate that pharmacological inhibition ETosis with Cl-amidine enhances repair, surpassing effects blocking recruitment. Simultaneously, treatment reshapes inflammatory response, causing neutrophils, helper, cytotoxic T-cells cluster primarily superficial capillary plexus, affecting microvasculature perfusion. data offer novel insights into immunity’s responding damage, potentially informing more effective immunotherapeutic strategies neurodegenerative diseases.

Language: Английский

Neutrophil extracellular traps in wound healing DOI
Zhanyong Zhu,

Shengzhi Zhou,

Sicheng Li

et al.

Trends in Pharmacological Sciences, Journal Year: 2024, Volume and Issue: 45(11), P. 1033 - 1045

Published: Oct. 16, 2024

Language: Английский

Citations

14
naRNA-LL37 composite DAMPs define sterile NETs as self-propagating drivers of inflammation DOI Creative Commons
Francesca Bork, Carsten Leo Greve, Christine Youn

et al.

EMBO Reports, Journal Year: 2024, Volume and Issue: 25(7), P. 2914 - 2949

Published: May 23, 2024

Language: Английский

Citations

9
Antimicrobial peptides and proteins against drug-resistant pathogens DOI Creative Commons

Y. C. Wang,

Minghui Song,

Wenqiang Chang

et al.

The Cell Surface, Journal Year: 2024, Volume and Issue: 12, P. 100135 - 100135

Published: Nov. 27, 2024

Language: Английский

Citations

7
Conductive Hydrogel Inspires Neutrophil Extracellular Traps to Combat Bacterial Infections in Wounds DOI Creative Commons

Lizhi Ouyang,

Ze Lin, Xi He

et al.

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

Thetreatment of infected wounds is currently a major challenge in clinical medicine, and enhancing antimicrobial angiogenic capacity one the most common strategies. However, current treatment makes it difficult to balance effect early stage later stages wound healing, leading an increased rate poor prognosis. Here, we present nanoconductive hydrogel EF@S-HGM, consisting HGM with ECGS, FMLP, SWCNT. The host-guest supramolecular macromolecule (HGM) biocompatible can be injected situ wound. endothelial cell growth factor (ECGS) accelerates vascular remodeling repairs by promoting proliferation cells. N-Formyl-Met-Leu-Phe (FMLP) recruits neutrophils increases capacity. Single-walled carbon nanotubes (SWCNT) make conductive, enabling utilize endogenous electric field recruit multiple kinds In addition, found that EF@S-HGM activates glucocorticoid receptor senescence pathway promotes formation NET, which enhances effect. As tissue-engineered skin, conductive promising material for regenerative medicine may provide potential option care significantly improve patient outcomes

Language: Английский

Citations

1
Macrophages coordinate immune response to laser-induced injury via extracellular traps DOI Creative Commons
Federica Maria Conedera, Despina Kokona, Martin S. Zinkernagel

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: March 18, 2024

Abstract Background Retinal degeneration results from disruptions in retinal homeostasis due to injury, disease, or aging and triggers peripheral leukocyte infiltration. Effective immune responses rely on coordinated actions of resident microglia recruited macrophages, critical for tissue remodeling repair. However, these phagocytes also contribute chronic inflammation degenerated retinas, yet the precise coordination response damage remains elusive. Recent investigations have demonstrated that phagocytic cells can produce extracellular traps (ETs), which are a source self-antigens alter response, potentially lead injury. Methods Innovations experimental systems facilitate real-time exploration cell interactions dynamic responses. We integrated vivo imaging with ultrastructural analysis, transcriptomics, pharmacological treatments, knockout mice elucidate role their modulation local inflammatory through (ETs). Deciphering mechanisms is essential developing novel enhanced immunotherapeutic approaches redirect specific maladaptive towards favorable wound healing retina. Results Our findings underscore pivotal innate cells, especially macrophages/monocytes, regulating repair inflammation. The absence neutrophil macrophage infiltration aids parenchymal integrity restoration, while depletion, particularly impedes vascular recovery. demonstrate when retina, release chromatin granular proteins, forming ETs. Furthermore, inhibition ETosis support repair, surpassing effects blocking recruitment. Simultaneously, reshapes causing neutrophils, helper, cytotoxic T-cells be restricted primarily superficial capillary plexus instead reaching damaged photoreceptor layer. Conclusions data offer insights into immunity's responding help innovative shift beneficial regeneration.

Language: Английский

Citations

5
Nets in fibrosis: Bridging innate immunity and tissue remodeling DOI
Xueni Ma,

LI Ji-pin,

Muyang Li

et al.

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 137, P. 112516 - 112516

Published: June 20, 2024

Language: Английский

Citations

3
Neutrophil-Leishmania infantum Interaction Induces Neutrophil Extracellular Traps, DAMPs, and Inflammatory Molecule Release DOI Creative Commons
Paulo Ricardo Porfírio do Nascimento,

Carolina O. Mendes-Aguiar,

Ingryd C. Morais

et al.

ACS Infectious Diseases, Journal Year: 2025, Volume and Issue: 11(2), P. 483 - 492

Published: Jan. 31, 2025

Neutrophils, the first cells to arrive at infection sites, release neutrophil extracellular traps (NETs) comprising nuclear and/or mitochondrial DNA webs decorated with proteins. Similar other parasites, Leishmania infantum induces NET extrusion. However, our understanding of formation and fate after in a context is limited. Our study aimed determine origin scaffolds released by human neutrophils response chemical or L. stimulation. Neutrophils were incubated PMA, PHA, LPS, infantum, followed elastase activity quantification; additionally, we evaluated source that composes NETs. Neutrophil viability was annexin-V/7AAd labeling. Expression IL6, TNFA, IL10, CXCL1, CXCL8, FPR1 interaction assessed. chemicals stimulated showed lower 1 h comparison parasites. NETs from chemically mainly composed DNA. Conversely, induced parasites had no leishmanicidal activity. After 4 parasite stimulation, peak expression genes such as FPR1. demonstrates produce exposure. Although they are not toxic parasite, danger signals. These findings support role releasing signaling molecules, which influence inflammatory environment infectious process occurs.

Language: Английский

Citations

0
Circulating Nucleosomes and Histones in the Development of Lung Injury and Sepsis DOI Creative Commons
Saugata Dutta, Saugata Dutta,

Payaningal R. Somanath

et al.

Current Issues in Molecular Biology, Journal Year: 2025, Volume and Issue: 47(2), P. 133 - 133

Published: Feb. 19, 2025

Cellular nucleosomes-the structural and functional units of chromatin-are inherently present in cells. During cellular damage or cell death, nucleosomes are released into circulation, either actively passively. Once released, can become immunogenic entities through various mechanisms. The nucleosomal proteins nucleosomes, called histones, play a pivotal role inducing immunogenicity. However, intact more than the histones alone, as double-stranded deoxyribonucleic acid (dsDNA) enhances its potential. Our recent study has shown that circulating predominantly rather free histones. Consequently, primarily function integral parts acting independently. Circulating their associated implicated pathogenesis wide array diseases. Notably, they critical lung injury sepsis. These diseases have high morbidity mortality rates lack early diagnostic biomarkers. Further investigation is required to fully elucidate disease processes. This review aims discuss current understanding sepsis, with focus on underlying

Language: Английский

Citations

0
Targeting tumor-associated neutrophils: A Promising Strategy in lung cancer Immunotherapy DOI Creative Commons
Yongjun Wang, Wang Li,

Zexu Wang

et al.

Cancer Pathogenesis and Therapy, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

0
Neutrophils Display Novel Partners of Cytosolic Proliferating Cell Nuclear Antigen Involved in Interferon Response in COVID-19 Patients DOI Creative Commons

Lucie Pesenti,

Rodrigo de Oliveira Formiga, Nicola Tamassia

et al.

Journal of Innate Immunity, Journal Year: 2025, Volume and Issue: 17(1), P. 154 - 175

Published: Feb. 27, 2025

Introduction: Neutrophils are key players in the hyperinflammatory response during SARS-CoV-2 infection. The cytosolic proliferating cell nuclear antigen (PCNA) is a scaffolding protein highly dependent on microenvironment status and known to interact with numerous proteins that regulate neutrophil functions. This study aimed examine content PCNA interactome neutrophils from COVID-19 patients. Methods: Proteomic analyses were performed cytosols healthy donors patients severe or critical COVID-19. In vitro approaches used explore biological significance of COVID-19-specific interactome. Results: Neutrophil cytosol analysis revealed strong interferon (IFN) signature, variations according disease severity. Interactome identified associations involved signaling, cytoskeletal organization, extracellular trap (NET) formation, such as arginine deiminase type-4 (PADI4) histone H3, particularly Functional studies signaling showed T2AA, scaffold inhibitor, downregulated IFN-related genes, including STAT1, MX1, IFIT1, IFIT2 neutrophils. Additionally, T2AA specifically inhibited secretion CXCL10, an IFN-dependent cytokine. was also found effector implicated NET especially cases. Conclusion: has unveiled new partners enhance pathway, thereby modulating immune responses contributing hyperinflammation These findings provide valuable insights into dysregulation other immune-related conditions.

Language: Английский

Citations

0