Impact of Changes in Human Airway Epithelial Cellular Composition and Differentiation on SARS-CoV-2 Infection Biology DOI Creative Commons
Melissa Thaler, Ying Wang, Anne M. van der Does

et al.

Journal of Innate Immunity, Journal Year: 2023, Volume and Issue: 15(1), P. 562 - 580

Published: Jan. 1, 2023

The consequences of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can range from asymptomatic to fatal disease. Variations in epithelial susceptibility SARS-CoV-2 depend on the anatomical location proximal distal tract. However, cellular biology underlying these variations is not completely understood. Thus, air-liquid interface cultures well-differentiated primary human tracheal and bronchial cells were employed study impact composition differentiation by transcriptional (RNA sequencing) immunofluorescent analyses. Changes investigated varying time or using specific compounds. We found that primarily infected only ciliated but also goblet transient secretory cells. Viral replication was impacted differences composition, which depended culturing origin. A higher percentage correlated a viral load. DAPT treatment, increased number reduced cells, decreased load, indicating contribution infection. Cell entry factors, especially cathepsin L transmembrane protease serine 2, affected time. In conclusion, our demonstrates changes related mucociliary system. This could explain part variable between individuals locations

Language: Английский

Regulation of angiotensin-converting enzyme 2 isoforms by type 2 inflammation and viral infection in human airway epithelium DOI Creative Commons
Nino Stocker, Urszula Radzikowska, Paulina Wawrzyniak

et al.

Mucosal Immunology, Journal Year: 2023, Volume and Issue: 16(1), P. 5 - 16

Published: Jan. 13, 2023

Language: Английский

Citations

16
From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID DOI Open Access
Pablo Gonzalez-Garcia, Ornella Fiorillo‐Moreno, Eloína Zarate Peñata

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8290 - 8290

Published: May 5, 2023

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given diversity characteristic cellular phenotype, possible cytopathic, and clinical effects are difficult predict, determines heterogeneity COVID-19 symptoms. The purpose this article provide a comprehensive review cytopathic SARS-CoV-2 on cell types, focusing development COVID-19, may lead, some patients, persistence symptoms after recovery disease, condition known as long COVID. We describe mechanisms underlying virus-host interactions, including alterations protein expression, intracellular signaling pathways, immune responses. In particular, highlights potential impact these cytopathies function outcomes, such dysregulation, neuropsychiatric disorders, organ damage. concludes discussing future directions for research implications management treatment

Language: Английский

Citations

16
Exposure to lung-migrating helminth protects against murine SARS-CoV-2 infection through macrophage-dependent T cell activation DOI
Oyebola O. Oyesola, Kerry L. Hilligan, Sivaranjani Namasivayam

et al.

Science Immunology, Journal Year: 2023, Volume and Issue: 8(86)

Published: Aug. 4, 2023

Helminth endemic regions report lower COVID-19 morbidity and mortality. Here, we show that lung remodeling from a prior infection with lung-migrating helminth, Nippostrongylus brasiliensis, enhances viral clearance survival of human-ACE2 transgenic mice challenged SARS-CoV-2 (SCV2). This protection is associated lymphocytic infiltrate, including increased accumulation pulmonary SCV2-specific CD8+ T cells, anti-CD8 antibody depletion abrogated the N. brasiliensis-mediated reduction in loads. Pulmonary macrophages type 2 transcriptional epigenetic signature persist lungs brasiliensis-exposed after parasite establish primed environment for cell recruitment activation. Accordingly, ablated augmented cells driven by brasiliensis infection. Together, these findings support concept helminths can limit disease severity during SCV2 through macrophage-dependent enhancement antiviral responses.

Language: Английский

Citations

16
Mucociliary transport deficiency and disease progression in Syrian hamsters with SARS-CoV-2 infection DOI Creative Commons
Qian Li, Kadambari Vijaykumar, Scott E. Phillips

et al.

JCI Insight, Journal Year: 2023, Volume and Issue: 8(1)

Published: Jan. 9, 2023

Substantial clinical evidence supports the notion that ciliary function in airways is important COVID-19 pathogenesis. Although damage has been observed both vitro and vivo models, extent or nature of impairment mucociliary transport (MCT) models remains unknown. We hypothesize SARS-CoV-2 infection results MCT deficiency golden Syrian hamsters precedes pathological injury lung parenchyma. Micro-optical coherence tomography was used to quantitate functional changes apparatus. Both genomic subgenomic viral RNA physiological were monitored parallel. show caused a 67% decrease rate as early 2 days postinfection (dpi) hamsters, principally due 79% diminished airway coverage motile cilia. Correlating quantitation physiological, virological, reveals steadily descending from upper lower parenchyma within 7 dpi. Our indicate deficits apparatus are key aspect pathogenesis, may extend retention, could pose risk factor for secondary infection. Clinically, monitoring abnormal ciliated cell disease progression. Therapies directed toward deserve further investigation.

Language: Английский

Citations

15
Type 2 inflammation reduces SARS-CoV-2 replication in the airway epithelium in allergic asthma through functional alteration of ciliated epithelial cells DOI
Naresh Doni Jayavelu, Matthew C. Altman, Basilin Benson

et al.

Journal of Allergy and Clinical Immunology, Journal Year: 2023, Volume and Issue: 152(1), P. 56 - 67

Published: March 29, 2023

Language: Английский

Citations

15
Chemosensory cells in the respiratory tract as crucial regulators of innate immune responses DOI Creative Commons
Monika I. Hollenhorst, Gabriela Krasteva‐Christ

The Journal of Physiology, Journal Year: 2023, Volume and Issue: 601(9), P. 1555 - 1572

Published: April 3, 2023

During recent years chemosensory cells in extraoral tissues have been established as mediators for the detection and regulation of innate immune processes response to pathogens. Under physiological conditions, are present throughout respiratory epithelium upper lower airways well main olfactory epithelium. Additionally, they emerge alveolar region lung upon viral infections. Chemosensory detect signalling molecules from gram-positive gram-negative bacteria aeroallergens fungi. Upon stimulation release multiple molecules, such transmitter acetylcholine, cysteinyl leukotriene E4 cytokine interleukin-25, which act autocrine paracrine signals thereby orchestrate responses system. Activation stimulates various cells, e.g. type 2 lymphoid modulates mucociliary clearance induces a protective neurogenic inflammation. This review compiles discusses findings regarding cell function tract.

Language: Английский

Citations

15
Synthesis and biological evaluation of novel peptidomimetic inhibitors of the coronavirus 3C-like protease DOI

Franck Amblard,

Julia C. LeCher,

Ramyani De

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 268, P. 116263 - 116263

Published: Feb. 24, 2024

Language: Английский

Citations

6
Machine learning to understand risks for severe COVID-19 outcomes: a retrospective cohort study of immune-mediated inflammatory diseases, immunomodulatory medications, and comorbidities in a large US health-care system DOI Creative Commons
Qi Wei, Philip J. Mease,

Michael Chiorean

et al.

The Lancet Digital Health, Journal Year: 2024, Volume and Issue: 6(5), P. e309 - e322

Published: April 24, 2024

In the context of immune-mediated inflammatory diseases (IMIDs), COVID-19 outcomes are incompletely understood and vary considerably depending on patient population studied. We aimed to analyse severe investigate effects pandemic time period risks associated with individual IMIDs, classes immunomodulatory medications (IMMs), chronic comorbidities, vaccination status.

Language: Английский

Citations

6
Cell Culture Differentiation and Proliferation Conditions Influence the In Vitro Regeneration of the Human Airway Epithelium DOI
Elisa Redman, Morgane Fierville,

Amélie Cavard

et al.

American Journal of Respiratory Cell and Molecular Biology, Journal Year: 2024, Volume and Issue: 71(3), P. 267 - 281

Published: June 6, 2024

The human airway mucociliary epithelium can be recapitulated

Language: Английский

Citations

5
NF-κB inhibitor alpha controls SARS-CoV-2 infection in ACE2-overexpressing human airway organoids DOI Creative Commons
Camille R. Simoneau, Peiyi Chen, Galen Xing

et al.

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: July 4, 2024

Abstract As SARS-CoV-2 continues to spread worldwide, tractable primary airway cell models that recapitulate the cell-intrinsic response arising viral variants are needed. Here we describe an adult stem cell-derived human organoid model overexpressing ACE2 receptor (ACE2-OE) supports robust replication while maintaining 3D architecture and cellular diversity of epithelium. ACE2-OE organoids were infected with subjected single-cell RNA-sequencing. Interferon-lambda was upregulated in cells low-level infection NF-kB inhibitor alpha gene (encoding IkBa) consistently cells, its expression positively correlated levels. Confocal microscopy showed more IkBa than bystander but found concurrent nuclear translocation usually prevents. Overexpressing a nondegradable mutant reduced increased infection. These data demonstrate functionality research underscore strength feedback loop controls replication.

Language: Английский

Citations

5