In vivo single-cell high-dimensional mass cytometry analysis to track the interaction betweenKlebsiella pneumoniaeand myeloid cells DOI Creative Commons
Ricardo Calderón-González, Amy Dumigan, Joana Sá‐Pessoa

et al.

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

Published: Dec. 14, 2023

ABSTRACT In vivo single-cell approaches have transformed our understanding of the immune populations in tissues. Mass cytometry (CyTOF), that combines resolution mass spectrometry with ability to conduct multiplexed measurements cell molecules at single resolution, has enabled resolve diversity subsets, and their heterogeneous functionality. Here we assess feasibility taking CyTOF one step further immuno profile cells while tracking interaction bacteria, a method term Bac-CyTOF. We focus on pathogen Klebsiella pneumoniae interrogating pneumonia mouse model. Using Bac-CyTOF, unveil atlas mice infected K. virulent strain. The is characterized by decrease alveolar macrophages monocyte-derived macrophages, whereas neutrophils, inflammatory monocytes are an increase subpopulations expressing markers characteristic less active such as checkpoint PD-L1. These those associated bacteria. show type VI secretion system (T6SS) contributes shape lung landscape. T6SS governs monocytes/macrophages shifting from interstitial limiting infection monocytes. Lack results cells, By infecting , Acinetobacter baumannii strains cleared mice, uncover heightened recruitment relative high levels eosinophils subpopulation neutrophils features clearing infections. Lastly, leverage Bac-CyTOF-generated knowledge platform investigate role DNA sensor STING sting −/− present including reduced absence facilitates clearance. AUTHOR SUMMARY Host-pathogen interactions vital infectious disease, well its treatment prevention. high-dimensional data analysis tremendous take this technology technology, following human . interacts these cells. contribution antimicrobial nanoweapon landscape, highlighting potential host defence. probing two pathogens effectively reveal infections successfully mice. There was no prior biology. Our findings suggest may utilize signalling for own benefit because

Language: Английский

Killing in the name of: T6SS structure and effector diversity DOI
Luke P. Allsopp, Patricia Bernal

Microbiology, Journal Year: 2023, Volume and Issue: 169(7)

Published: July 25, 2023

The life of bacteria is challenging, to endure employ a range mechanisms optimize their environment, including deploying the type VI secretion system (T6SS). Acting as bacterial crossbow, this delivers effectors responsible for subverting host cells, killing competitors and facilitating general access common goods. Due its importance, lethal machine has been evolutionarily maintained, disseminated specialized fulfil these vital functions. In fact, T6SS structural clusters are present in over 25 % Gram-negative bacteria, varying number from one six different genetic per organism. Since discovery 2006, research on rapidly progressed, yielding remarkable breakthroughs. identification characterization novel components T6SS, combined with biochemical studies, have revealed fascinating governing assembly, loading, firing disassembly processes. Recent findings also demonstrated efficacy against fungal Gram-positive expanding scope. Ongoing continues uncover an extensive repertoire effectors, genuine mediators function. These studies shedding light new aspects biology prokaryotic eukaryotic organisms. This review provides comprehensive overview highlighting recent discoveries structure diversity effectors. Additionally, it injects personal perspective avenues future research, aiming deepen our understanding combative system.

Language: Английский

Citations

35
In vivo single-cell high-dimensional mass cytometry analysis to track the interactions between Klebsiella pneumoniae and myeloid cells DOI Creative Commons
Ricardo Calderón-González, Amy Dumigan, Joana Sá‐Pessoa

et al.

PLoS Pathogens, Journal Year: 2024, Volume and Issue: 20(4), P. e1011900 - e1011900

Published: April 5, 2024

In vivo single-cell approaches have transformed our understanding of the immune populations in tissues. Mass cytometry (CyTOF), that combines resolution mass spectrometry with ability to conduct multiplexed measurements cell molecules at single resolution, has enabled resolve diversity subsets, and their heterogeneous functionality. Here we assess feasibility taking CyTOF one step further immuno profile cells while tracking interactions bacteria, a method term Bac-CyTOF. We focus on pathogen Klebsiella pneumoniae interrogating pneumonia mouse model. Using Bac-CyTOF, unveil atlas mice infected K . hypervirulent strain. The is characterized by decrease alveolar monocyte-derived macrophages. Conversely, neutrophils, inflammatory monocytes are an increase subpopulations expressing markers less active such as checkpoint PD-L1. These infected. show type VI secretion system (T6SS) contributes shape lung landscape. T6SS governs interaction monocytes/macrophages shifting from macrophages interstitial limiting infection monocytes. lack results cells, By probing , Acinetobacter baumannii strains limited survive vivo, uncover heightened recruitment relative high levels eosinophils characteristic subpopulation neutrophils features clearing infections. leverage Bac-CyTOF-generated knowledge platform investigate role DNA sensor STING sting -/- present consistent including reduced absence facilitates clearance.

Language: Английский

Citations

5
NLRX1: Versatile functions of a mitochondrial NLR protein that controls mitophagy DOI Creative Commons

Paul Y. Bi,

Samuel A. Killackey, Linus Schweizer

et al.

Biomedical Journal, Journal Year: 2023, Volume and Issue: 47(1), P. 100635 - 100635

Published: Aug. 11, 2023

NLRX1 is a member of the Nod-like receptor (NLR) family, and it represents unique pattern recognition molecule (PRM) as localizes to mitochondrial matrix in resting conditions. Over past fifteen years, has been proposed regulate multiple cellular processes, including antiviral immunity, apoptosis, reactive oxygen species (ROS) generation metabolism. Similarly, vivo models have shown that was associated with control number diseases, sclerosis, colorectal cancer ischemia-reperfusion injury. This apparent versatility function hinted common general overarching role for may exist. Recent evidence suggested controls mitophagy through detection specific "danger signal", namely defective import proteins into mitochondria, or protein stress (MPIS). In this review article, we propose regulation represent process detected by NLRX1, which could turn impact on diseases if dysfunctional.

Language: Английский

Citations

11
Klebsiella pneumoniae emerging anti-immunology paradigms: from stealth to evasion DOI Creative Commons
Joana Sá‐Pessoa, Ricardo Calderón-González,

Alix Lee

et al.

Trends in Microbiology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Klebsiella pneumoniae (KP) is a global threat to human health due the isolation of multidrug-resistant strains. Despite advancements in understanding KP's population structure, antibiotic resistance mechanisms, and transmission patterns, gap remains how KP evades defenses, allowing pathogen flourish tissues despite an activated immune system. infection biology has been shaped by notion that evolved shield from defenses more than actively suppress them. This review describes new paradigms exploits coevolution with innate system hijack effectors receptors ablate signaling pathways counteract cell-intrinsic immunity, making apparent can no longer be considered only as stealth pathogen.

Language: Английский

Citations

0
Broad-spectrum anti-inflammatory and antioxidant therapy of inflammatory-storm actuated diseases via programmable self-derived cryo-dead neutrophils DOI
Bin Li,

Qiuxia Gao,

Yunxia Wu

et al.

Chemical Engineering Journal, Journal Year: 2025, Volume and Issue: unknown, P. 160643 - 160643

Published: Feb. 1, 2025

Language: Английский

Citations

0
Experimental Approaches to Visualize Effector Protein Translocation During Host‐Pathogen Interactions DOI Creative Commons
Verena Nadin Fritsch, Michael Hensel

BioEssays, Journal Year: 2025, Volume and Issue: unknown

Published: March 13, 2025

ABSTRACT Bacterial pathogens deliver effector proteins into host cells by deploying sophisticated secretion systems. This translocation during host‐pathogen interactions is a prerequisite for the manipulation of and organisms important pathogenesis. Analyses dynamics kinetics translocation, subcellular localization, cellular targets lead to understanding mode action function in interplay. review provides an overview biochemical genetic tools that have been developed study protein qualitatively or quantitatively. After introducing challenges analyses interaction, we describe various methods ranging from static visualization fixed dynamic live‐cell imaging translocation. We show main findings enabled approaches, emphasize advantages limitations methods, recent approaches allow real‐time tracking living on single molecule level, highlight open questions field be addressed application new methods.

Language: Английский

Citations

0
Insights into the roles of macrophages in Klebsiella pneumoniae infections: a comprehensive review DOI Creative Commons
Yangguang Li,

Xuanheng Li,

Wenqi Wu

et al.

Cellular & Molecular Biology Letters, Journal Year: 2025, Volume and Issue: 30(1)

Published: March 26, 2025

Abstract Klebsiella pneumoniae (KP) infections represent a significant global health challenge, characterized by severe inflammatory sequelae and escalating antimicrobial resistance. This comprehensive review elucidates the complex interplay between macrophages KP, encompassing pathogen recognition mechanisms, macrophage activation states, cellular death pathways, emerging immunotherapeutic strategies. We critically analyze current literature on pattern receptor engagement with KP-associated molecular patterns. The examines spectrum of responses to KP infection, including classical M1 polarization newly described M(Kp) phenotype, alongside metabolic reprogramming events such as glycolytic enhancement immune responsive gene 1 (IRG1)–itaconate upregulation. systematically evaluate fate decisions in response autophagy, apoptosis, pyroptosis, necroptosis. Furthermore, we provide critical assessment potential future therapeutic modalities. Given limitations treatment paradigms, elucidating macrophage–KP interactions is imperative. Insights gained from this analysis may inform development novel immunomodulatory approaches augment conventional therapies, potentially transforming clinical management infections. Graphical

Language: Английский

Citations

0
Host–microbe interactions in the lung and the role of immunometabolism DOI
Sebastián Riquelme-Barrios, Ayesha Zainab Beg, Tania Wong Fok Lung

et al.

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 7 - 26

Published: Jan. 1, 2025

Language: Английский

Citations

0
The role of pyroptosis in environmental pollutants-induced multisystem toxicities DOI
Rui Xu, Longfei Li,

Yijia Ke

et al.

Life Sciences, Journal Year: 2025, Volume and Issue: 372, P. 123632 - 123632

Published: April 10, 2025

Language: Английский

Citations

0
Klebsiella pneumoniae disrupts vasodilation by targeting eNOS post translational modifications via the type VI secretion system and the capsule polysaccharide DOI Creative Commons
Safi Rehman, Joana Sá‐Pessoa, Charlotte Buckley

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

SUMMARY Vasodilation is a crucial protective response to inflammation and infection. Endothelial cells control vasodilation through the bioavailability of eNOS-produced nitric oxide (NO), generation endothelium-dependent hyperpolarization (EDH). Here, we demonstrate that Klebsiella pneumoniae , one most prevalent blood stream infection pathogens, inhibits agonist-induced by blunting NO-dependent pathway attenuating EDH pathway. The type VI secretion system (T6SS) effector VgrG4 licences kinase PKCβ in an NLRX1-controlled mitochondria reactive oxygen species (mtROS)-dependent manner phosphorylate eNOS inhibitory site Thr 495 effectively dampening activity. capsule polysaccharide, on other hand, limits phosphorylation activation Ser 1177 inducing phosphatase PP2Ac upon EGF receptor-dependent VgrG4-induced mtROS attenuates Overall, this work reveals new anti-host activity T6SS illustrates how pathogens can vascular biology targeting post translational modifications.

Language: Английский

Citations

0