A novel mouse model for the investigation of adaptive immune responses upon de novo antigen expression in lung epithelial cells

Pneumologie ◽  
2014 ◽  
Vol 68 (06) ◽  
Author(s):  
M Riehn ◽  
M Cebula ◽  
A Ochel ◽  
P Gaur ◽  
H Hauser ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Mouse Model ◽  
Immune Responses ◽  
De Novo ◽  
Antigen Expression ◽  
Lung Epithelial Cells ◽  
Adaptive Immune Responses ◽  
Adaptive Immune ◽  
Lung Epithelial

scholarly journals Effect of Slit/Robo signaling on regeneration in lung emphysema

2021 ◽  
Author(s):  
Jin-Soo Park ◽  
RyeonJin Cho ◽  
Eun-Young Kang ◽  
Yeon-Mok Oh
Keyword(s):  
Epithelial Cells ◽  
Mouse Model ◽  
Lung Epithelial Cells ◽  
Mouse Lung ◽  
Chronic Obstructive ◽  
Irreversible Damage ◽  
Lung Epithelial ◽  
And Migration ◽  
Proliferation And Migration

AbstractEmphysema, a pathological component of chronic obstructive pulmonary disease, causes irreversible damage to the lung. Previous studies have shown that Slit plays essential roles in cell proliferation, angiogenesis, and organ development. In this study, we evaluated the effect of Slit2 on the proliferation and migration of mouse lung epithelial cells and its role in regeneration in an emphysema lung mouse model. Here, we have shown that Slit2/Robo signaling contributes to the regeneration of lungs damaged by emphysema. Mouse epithelial lung cells treated with Slit2 exhibited increased proliferation and migration in vitro. Our results also showed that Slit2 administration improved alveolar regeneration in the emphysema mouse model in vivo. Furthermore, Slit2/Robo signaling increased the phosphorylation of ERK and Akt, which was mediated by Ras activity. These Slit2-mediated cellular signaling processes may be involved in the proliferation and migration of mouse lung epithelial cells and are also associated with the potential mechanism of lung regeneration. Our findings suggest that Slit2 administration may be beneficial for alveolar regeneration in lungs damaged by emphysema.

scholarly journals Mifepristone (RU486) inducing abortion in a mouse model by regulating innate and adaptive immune responses

2020 ◽  
Vol 4 (2) ◽  
pp. 63
Author(s):  
Yan-Hong Li ◽  
Mei-Rong Du ◽  
Meng-Die Li ◽  
Yi-Fei Sang ◽  
Yun-Hui Tang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Immune Responses ◽  
Adaptive Immune Responses ◽  
Adaptive Immune

Lung epithelial cells interact with immune cells and bacteria to shape the microenvironment in tuberculosis

Thorax ◽  
2022 ◽  
pp. thoraxjnl-2021-217997
Author(s):  
Amy M de Waal ◽  
Pieter S Hiemstra ◽  
Tom HM Ottenhoff ◽  
Simone A Joosten ◽  
Anne M van der Does
Keyword(s):  
Epithelial Cells ◽  
Immune Cells ◽  
Lung Epithelial Cells ◽  
Lung Epithelium ◽  
Adaptive Immune ◽  
Adaptive Immune Cells ◽  
Essential Components ◽  
Lung Epithelial ◽  
Sense And Respond ◽  
Tuberculosis Disease

The lung epithelium has long been overlooked as a key player in tuberculosis disease. In addition to acting as a direct barrier to Mycobacterium tuberculosis (Mtb), epithelial cells (EC) of the airways and alveoli act as first responders during Mtb infections; they directly sense and respond to Mtb by producing mediators such as cytokines, chemokines and antimicrobials. Interactions of EC with innate and adaptive immune cells further shape the immune response against Mtb. These three essential components, epithelium, immune cells and Mtb, are rarely studied in conjunction, owing in part to difficulties in coculturing them. Recent advances in cell culture technologies offer the opportunity to model the lung microenvironment more closely. Herein, we discuss the interplay between lung EC, immune cells and Mtb and argue that modelling these interactions is of key importance to unravel early events during Mtb infection.

scholarly journals The Inability of Wild-Type Rabies Virus To Activate Dendritic Cells Is Dependent on the Glycoprotein and Correlates with Its Low Level of theDe Novo-Synthesized Leader RNA

2014 ◽  
Vol 89 (4) ◽  
pp. 2157-2169 ◽  
Author(s):  
Yang Yang ◽  
Ying Huang ◽  
Clement W. Gnanadurai ◽  
Shengbo Cao ◽  
Xueqin Liu ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Rabies Virus ◽  
Adoptive Transfer ◽  
Viral Infections ◽  
De Novo ◽  
Wild Type ◽  
Adaptive Immune Responses ◽  
Low Level ◽  
Adaptive Immune

ABSTRACTDendritic cells (DCs) are the most efficient antigen-presenting cells, playing a key role in the adaptive immune responses to viral infections. Our studies demonstrate that wild-type (wt) rabies virus (RABV) does not activate DCs. Adoptive transfer of DCs primed with wt RABV did not activate DCs, stimulate virus neutralizing antibodies (VNA), or protect recipients against challenge. However, adoptive transfer of DCs primed with laboratory-attenuated RABV resulted in DC activation, production of VNA, and protection against challenge.In vitrostudies with recombinant RABV (laboratory-attenuated RABV expressing the glycoprotein or the phosphoprotein from wt RABV) demonstrate that DC activation is dependent on the glycoprotein and involves the IPS-1 pathway. Furthermore, binding to and entry into DCs by wt RABV is severely blocked, and the copy number ofde novo-synthesized leader RNA was two logs lower in DCs infected with the wt than in DCs treated with laboratory-attenuated RABV. However, transient transfection of DCs with synthesized leader RNA from either wt or attenuated RABV is capable of activating DCs in a dose-dependent manner. Thus, the inability of wt RABV to activate DCs correlates with its low level of thede novo-synthesized leader RNA.IMPORTANCERabies remains a public health threat, with more than 55,000 fatalities each year around the world. Since DCs play a key role in the adaptive immune responses to viral infections, we investigated the ability of rabies virus (RABV) to activate DCs. It was found that the adoptive transfer of DCs primed with wt RABV did not activate DCs, stimulate VNA, or protect mice against lethal challenge. However, laboratory-attenuated RABV mediates the activation of DCs via the IPS-1 pathway and is glycoprotein dependent. We further show that wt RABV evades DC-mediated immune activation by inefficient binding/entry into DCs and as a result of a reduced level ofde novo-synthesized leader RNA. These findings may have important implications in the development of efficient rabies vaccines.

scholarly journals Human neutrophil peptides induce interleukin-8 production through the P2Y6 signaling pathway

Blood ◽  
2006 ◽  
Vol 107 (7) ◽  
pp. 2936-2942 ◽  
Author(s):  
Aye Aye Khine ◽  
Lorenzo Del Sorbo ◽  
Rosanna Vaschetto ◽  
Stefanos Voglis ◽  
Elizabeth Tullis ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Responses ◽  
Signaling Pathway ◽  
Human Neutrophil ◽  
P2y Receptors ◽  
Interleukin 8 ◽  
Lung Epithelial Cells ◽  
Uridine Diphosphate ◽  
Immature Dendritic Cells ◽  
Lung Epithelial

AbstractAntimicrobial human neutrophil peptides (HNPs) play a pivotal role in innate host defense against a broad spectrum of prokaryotic pathogens. In addition, HNPs modulate cellular immune responses by producing the chemokine interleukin-8 (IL-8) in myeloid and epithelial cells and by exerting chemotaxis to T cells, immature dendritic cells, and monocytes. However, the mechanisms by which HNPs modulate the immune responses in the eukaryotic cells remain unclear. We demonstrated that, as with adenosine triphosphate (ATP) and uridine diphosphate (UDP), HNP stimulation of human lung epithelial cells selectively induced IL-8 production in 10 pro- and anti-inflammatory cytokines examined. HNP-induced IL-8 release was inhibited by treatment with the nucleotide receptor antagonists suramin and reactive blue. Transfection of lung epithelial cells with antisense oligonucleotides targeting specific purinergic P2Y receptors revealed that the P2Y6 (ligand of UDP) signaling pathway plays a predominant role in mediating HNP-induced IL-8 production.

Apoptosis of lung epithelial cells in response to TNF-? requires angiotensin II generation de novo

2000 ◽  
Vol 185 (2) ◽  
pp. 253-259 ◽  
Author(s):  
Rongqi Wang ◽  
Golam Alam ◽  
Alex Zagariya ◽  
Claudia Gidea ◽  
Hugo Pinillos ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Epithelial Cells ◽  
De Novo ◽  
Lung Epithelial Cells ◽  
Lung Epithelial

scholarly journals SARS-CoV-2 triggers an MDA-5-dependent interferon response which is unable to control replication in lung epithelial cells

2021 ◽  
Author(s):  
Antoine Rebendenne ◽  
Ana Luiza Chaves Valadão ◽  
Marine Tauziet ◽  
Ghizlane Maarifi ◽  
Boris Bonaventure ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Viral Replication ◽  
Mammalian Cells ◽  
De Novo ◽  
Etiologic Agent ◽  
Lung Epithelial Cells ◽  
Interferon Response ◽  
Lung Cells ◽  
Type I ◽  
Lung Epithelial

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the etiologic agent of coronavirus disease 19 (COVID-19), which ranges from mild respiratory symptoms to acute respiratory distress syndrome, and death in the most severe cases. Immune dysregulation with altered innate cytokine responses is thought to contribute to disease severity. Here, we characterized in depth host cell responses against SARS-CoV-2 in primary human airway epithelia (HAE) and immortalized cell lines. Our results demonstrate that primary HAE and model cells elicit a robust induction of type I and III interferons (IFNs). Importantly, we show for the first time that melanoma differentiation associated gene (MDA)-5 is the main sensor of SARS-CoV-2 in lung cells. IFN exposure strongly inhibited viral replication and de novo production of infectious virions. However, despite high levels of IFNs produced in response to SARS-CoV-2 infection, the IFN response was unable to control viral replication in lung cells, contrary to what was previously reported in intestinal epithelial cells. Altogether, these results highlight the complex and ambiguous interplay between viral replication and the timing of IFN responses. IMPORTANCE Mammalian cells express sensors able to detect specific features of pathogens and induce the interferon response, which is one of the first line of defenses against viruses and help controlling viral replication. The mechanisms and impact of SARS-CoV-2 sensing in lung epithelial cells remained to be deciphered. In this study, we report that despite a high production of type I and III interferons specifically induced by MDA-5-mediated sensing of SARS-CoV-2, primary and immortalized lung epithelial cells are unable to control viral replication. However, exogenous interferons potently inhibited replication, if provided early upon viral exposure. A better understanding of the ambiguous interplay between the interferon response and SARS-CoV-2 replication is essential to guide future therapeutical interventions.

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