IL-1β-driven NF-κB transcription of ACE2 as a Mechanism of Macrophage Infection by SARS-CoV-2 DOI Creative Commons
Cadence Lee, Rachel E. Khan, Chris S Mantsounga

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 26, 2024

ABSTRACT Coronavirus disease 2019 (COVID-19), caused by infection with the enveloped RNA betacoronavirus, SARS-CoV-2, led to a global pandemic involving over 7 million deaths. Macrophage inflammatory responses impact COVID-19 severity; however, it is unclear whether macrophages are infected SARS-CoV-2. We sought identify mechanisms regulating macrophage expression of ACE2, primary receptor for and determine if susceptible productive infection. developed humanized ACE2 ( hACE2 ) mouse whereby cDNA was cloned into locus under control native promoter. validated susceptibility mice SARS-CoV-2 relative wild-type an established K18-hACE2 model acute fulminating disease. Intranasal exposure pulmonary consolidations cellular infiltrate, edema, hemorrhage, consistent pneumonia, yet unlike model, survived maintained stable weight. Infected also exhibited unique plasma chemokine, cytokine, growth factor signature mice. demonstrated evidence viral replication in infiltrating lung macrophages, vitro revealed transcriptional profile indicative altered ribosomal processing machinery as well activated antiviral defense. IL-1β-driven NF-κB transcription important mechanism dynamic upregulation, promoting Experimental models that make use will allow mechanistic insight factors can either promote host resilience or increase worsening severity

Language: Английский

SARS-CoV-2 infection drives an inflammatory response in human adipose tissue through infection of adipocytes and macrophages DOI Creative Commons
Giovanny J. Martínez-Colón, Kalani Ratnasiri, Richard Chen

et al.

Science Translational Medicine, Journal Year: 2022, Volume and Issue: 14(674)

Published: Sept. 22, 2022

Obesity, characterized by chronic low-grade inflammation of the adipose tissue, is associated with adverse coronavirus disease 2019 (COVID-19) outcomes, yet underlying mechanism unknown. To explore whether severe acute respiratory syndrome 2 (SARS-CoV-2) infection tissue contributes to pathogenesis, we evaluated COVID-19 autopsy cases and deeply profiled response SARS-CoV-2 in vitro. In cases, identified RNA adipocytes an inflammatory infiltrate. We two distinct cellular targets infection: a subset tissue-resident macrophages. Mature were permissive infection; although macrophages abortively infected, initiated responses within both infected bystander preadipocytes. These data suggest that could contribute severity through replication virus induction local systemic driven

Language: Английский

Citations

87
Precision cut lung slices: an integrated ex vivo model for studying lung physiology, pharmacology, disease pathogenesis and drug discovery DOI Creative Commons
Cynthia Koziol‐White, Eric Gebski,

Gaoyaun Cao

et al.

Respiratory Research, Journal Year: 2024, Volume and Issue: 25(1)

Published: June 1, 2024

Precision Cut Lung Slices (PCLS) have emerged as a sophisticated and physiologically relevant ex vivo model for studying the intricacies of lung diseases, including fibrosis, injury, repair, host defense mechanisms. This innovative methodology presents unique opportunity to bridge gap between traditional in vitro cell cultures animal models, offering researchers more accurate representation intricate microenvironment lung. PCLS require precise sectioning tissue maintain its structural functional integrity. These thin slices serve invaluable tools various research endeavors, particularly realm airway diseases. By providing controlled microenvironment, precision-cut empower dissect comprehend multifaceted interactions responses within tissue, thereby advancing our understanding pulmonary pathophysiology.

Language: Английский

Citations

12
B cells modulate lung antiviral inflammatory responses via the neurotransmitter acetylcholine DOI Creative Commons

Antonio Cembellin-Prieto,

Zheng Luo,

Heather Kulaga

et al.

Nature Immunology, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

Abstract The rapid onset of innate immune defenses is critical for early control viral replication in an infected host and yet it can also lead to irreversible tissue damage, especially the respiratory tract. Sensitive regulators must exist that modulate inflammation, while controlling infection. In present study, we identified acetylcholine (ACh)-producing B cells as such regulators. are most prevalent ACh-producing leukocyte population tract demonstrated with choline acetyltransferase (ChAT)-green fluorescent protein (GFP) reporter mice, both before after infection influenza A virus. Mice lacking ChAT cells, disabling their ability generate ACh (ChatBKO), but not those T significantly, selectively directly suppressed α7-nicotinic-ACh receptor-expressing interstitial, alveolar, macrophage activation secrete tumor necrosis factor (TNF), better virus at 1 d postinfection. Conversely, TNF blockade via monoclonal antibody treatment increased loads time. By day 10 infection, ChatBKO mice showed local systemic inflammation reduced signs lung epithelial repair despite similar clearance. Thus, key participants immediate regulatory cascade controls damage shifting balance toward cost enhanced replication.

Language: Английский

Citations

1
Nanoscale cellular organization of viral RNA and proteins in SARS-CoV-2 replication organelles DOI Creative Commons
Leonid Andronov, Mengting Han, Yan‐Yu Zhu

et al.

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: May 31, 2024

Abstract The SARS-CoV-2 viral infection transforms host cells and produces special organelles in many ways, we focus on the replication organelles, sites of genomic RNA (vgRNA). To date, precise cellular localization key molecules intermediates has been elusive electron microscopy studies. We use super-resolution fluorescence specific labeling to reveal nanoscopic organization that contain numerous vgRNA along with enzymes clusters double-stranded (dsRNA). show are organized differently at early late stages infection. Surprisingly, accumulates into distinct globular cytoplasmic perinuclear region, which grow accommodate more as time increases. endoplasmic reticulum (ER) markers nsp3 (a component double-membrane vesicle, DMV) periphery suggests encapsulated DMVs, have membranes derived from ER. These merge larger vesicle packets advances. Precise co-imaging nanoscale vgRNA, dsRNA, proteins may inform therapeutic approaches target associated processes.

Language: Английский

Citations

6
The Importance of Lung Innate Immunity During Health and Disease DOI Creative Commons
Gusty Rizky Teguh Ryanto, Ratoe Suraya, Tatsuya Nagano

et al.

Pathogens, Journal Year: 2025, Volume and Issue: 14(1), P. 91 - 91

Published: Jan. 17, 2025

The lung is a vital organ for the body as main source of oxygen input. Importantly, it also an internal that has direct contact with outside world. Innate immunity protective system in various organs, whereas, case lung, helps maintain healthy, functioning cellular and molecular environment prevents any overt damage caused by pathogens or other inflammatory processes. Disturbances innate properties processes, whether over-responsiveness process triggered lack responses due to dysfunctions immune cells make up could be correlated pathological conditions. In this review, we discuss globally how components are important not only maintaining homeostasis but during pathophysiology notable diseases beyond acute pulmonary infections, including chronic obstructive disease (COPD), asthma, fibrosis.

Language: Английский

Citations

0
Exploring CD169+ Macrophages as Key Targets for Vaccination and Therapeutic Interventions DOI Creative Commons
Rianne G. Bouma,

Aru Z. Wang,

Joke M. M. den Haan

et al.

Vaccines, Journal Year: 2025, Volume and Issue: 13(3), P. 330 - 330

Published: March 20, 2025

CD169 is a sialic acid-binding immunoglobulin-like lectin (Siglec-1, sialoadhesin) that expressed by subsets of tissue-resident macrophages and circulating monocytes. This receptor interacts with α2,3-linked Neu5Ac on glycoproteins as well glycolipids present the surface immune cells pathogens. CD169-expressing exert tissue-specific homeostatic functions, but they also have opposing effects response. CD169+ act pathogen filter, protect against infectious diseases, enhance adaptive immunity, at same time pathogens exploit them to enable further dissemination. In cancer, in tumor-draining lymph nodes are correlated better clinical outcomes. inflammatory expression upregulated monocytes monocyte-derived this correlates disease state. Given their role promoting currently investigated targets for vaccination strategies cancer. review, we describe studies investigating importance several settings under investigation.

Language: Английский

Citations

0
Lung tumor immunity: redirecting macrophages through infection-induced inflammation DOI Creative Commons

Öznur Aktay-Cetin,

Soni Savai Pullamsetti, Susanne Herold

et al.

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

Published: May 1, 2025

Language: Английский

Citations

0
Single cell RNA-seq: a novel tool to unravel virus-host interplay DOI

Harsh Rajeshbhai Jogi,

Nabaneeta Smaraki,

Sonali Sonejita Nayak

et al.

VirusDisease, Journal Year: 2024, Volume and Issue: 35(1), P. 41 - 54

Published: March 1, 2024

Language: Английский

Citations

2
Spatiotemporal analysis of lung immune dynamics in lethal Coccidioides posadasii infection DOI Creative Commons
Oscar A. Davalos, Aimy Sebastian, Nicole F. Leon

et al.

mBio, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 29, 2024

ABSTRACT Coccidioidomycosis, or Valley fever, is a lung disease caused by inhalation of Coccidioides fungi, prevalent in the Southwestern United States, Mexico, and parts Central South America. Annually, States reports 10,000–20,000 cases, although those numbers are expected to increase as climate change expands fungal geographic range. While 60% infections asymptomatic, 40% symptomatic often misdiagnosed due similarities with bronchitis pneumonia. A small subset infection progress severe illness, necessitating better understanding immune responses during lethal infection. Using single-cell RNA sequencing spatial transcriptomics, we characterized We identified monocyte-derived Spp1 -expressing macrophages potential mediators tissue remodeling fibrosis, marked high expression profibrotic proinflammatory transcripts. These showed elevated TGF-β IL-6 signaling, pathways involved fibrosis pathogenesis. Additionally, observed significant neutrophil infiltration defective lymphocyte responses, indicating adaptive immunity dysregulation lethal, acute findings enhance our suggest new therapeutic targets. IMPORTANCE commonly known which With potentially expanding range this fungus, crucial. Our study used advanced techniques analyze infection, identifying specific cells that may contribute damage fibrosis. provide insights into mechanisms targets for intervention, could improve outcomes patients suffering from fever.

Language: Английский

Citations

2
Computational Modeling of Transformations of Epidemic Waves of BA.2.86/JN.1 SAR-COV-2 Coronavirus Variants on the Basis of Hybrid Oscillators DOI
A. Yu. Perevaryukha

Technical Physics, Journal Year: 2024, Volume and Issue: unknown

Published: July 12, 2024

Language: Английский

Citations

2