scholarly journals Host signaling and proteolytic pathways in the resolution or the exacerbation of coronavirus (CoV-2) infection in COVID-19 disease: what therapeutic targets?

2020 ◽  
Author(s):  
Jean-Michel SALLENAVE ◽  
Loic Guillot
Keyword(s):  
Immune Responses ◽  
Serine Proteases ◽  
Multiple Organ ◽  
Innate Immune ◽  
Alveolar Epithelial Cells ◽  
Innate Immune Responses ◽  
Dipeptidyl Peptidase 4 ◽  
Alveolar Epithelial ◽  
Enveloped Virus ◽  
Host Signaling

COVID-19 is caused by the Severe Acute Respiratory Syndrome (SARS) coronavirus (Cov)-2, an enveloped virus with a positive single-stranded RNA genome. Pandemic initial outbreak began in December 2019 and is threatening the health of the global community. In common with previous pandemics (Influenza H1N1, SARS-CoV-1) and the epidemics of Middle east respiratory syndrome (MERS)-CoV, CoVs target bronchial and alveolar epithelial cells. Virus proteins ligands (eg haemagglutinin or spike protein for Influenza and CoV, respectively) interact with cellular receptors such as (depending on the virus), either sialic acids, Dipeptidyl peptidase 4 (DPP4), or angiotensin-converting enzyme 2 (ACE2). Host proteases, eg cathepsins, furin, or members of the type II transmembrane serine proteases (TTSP) family such as Transmembrane protease serine 2 (TMPRSS2) are involved in virus entry by proteolytically activating virus ligands. Also involved are Toll Like Receptor (TLR) familly members which up-regulate anti-viral and pro-inflammatory mediators (interleukin (IL)-6 and IL-8...), through the activation of Nuclear Factor (NF)-kB. When these events (virus cellular entry and innate immune responses) are uncontrolled, a deleterious systemic response is sometimes encountered in infected patients, leading to the well described ‘cytokine storm’ and an ensuing multiple organ failure, promoted by a down-regulation of dendritic cells, macrophage and T cell function.We aim to describe how the lung and systemic host innate immune responses affect survival either positively, through down-regulating initial viral load, or negatively, by triggering uncontrolled inflammation. An emphasis will be put on host cellular signaling pathways and proteases involved, with a view on tackling these therapeutically.

scholarly journals Type I Alveolar Epithelial Cells Mount Innate Immune Responses during Pneumococcal Pneumonia

2012 ◽  
Vol 189 (5) ◽  
pp. 2450-2459 ◽  
Author(s):  
Kazuko Yamamoto ◽  
Joseph D. Ferrari ◽  
Yuxia Cao ◽  
Maria I. Ramirez ◽  
Matthew R. Jones ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Responses ◽  
Pneumococcal Pneumonia ◽  
Innate Immune ◽  
Alveolar Epithelial Cells ◽  
Type I ◽  
Innate Immune Responses ◽  
Alveolar Epithelial

Innate Immune Responses Of Type I Alveolar Epithelial Cells During Pneumonia

2012 ◽  
Author(s):  
Kazuko Yamamoto ◽  
Joseph D. Ferrari ◽  
Maria I. Ramirez ◽  
Matthew R. Jones ◽  
Lee J. Quinton ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Responses ◽  
Innate Immune ◽  
Alveolar Epithelial Cells ◽  
Type I ◽  
Innate Immune Responses ◽  
Alveolar Epithelial

scholarly journals Influenza induces IL-8 and GM-CSF secretion by human alveolar epithelial cells through HGF/c-Met and TGF-α/EGFR signaling

2015 ◽  
Vol 308 (11) ◽  
pp. L1178-L1188 ◽  
Author(s):  
Yoko Ito ◽  
Kelly Correll ◽  
Rachel L. Zemans ◽  
Christina C. Leslie ◽  
Robert C. Murphy ◽  
...  
Keyword(s):  
Growth Factor ◽  
Epithelial Cells ◽  
Immune Responses ◽  
Influenza Infection ◽  
Innate Immune ◽  
Alveolar Epithelial Cells ◽  
Innate Immune Responses ◽  
Egfr Signaling ◽  
Alveolar Epithelial ◽  
Gm Csf

The most severe complication of influenza is viral pneumonia, which can lead to the acute respiratory distress syndrome. Alveolar epithelial cells (AECs) are the first cells that influenza virus encounters upon entering the alveolus. Infected epithelial cells produce cytokines that attract and activate neutrophils and macrophages, which in turn induce damage to the epithelial-endothelial barrier. Hepatocyte growth factor (HGF)/c-Met and transforming growth factor-α (TGF-α)/epidermal growth factor receptor (EGFR) are well known to regulate repair of damaged alveolar epithelium by stimulating cell migration and proliferation. Recently, TGF-α/EGFR signaling has also been shown to regulate innate immune responses in bronchial epithelial cells. However, little is known about whether HGF/c-Met signaling alters the innate immune responses and whether the innate immune responses in AECs are regulated by HGF/c-Met and TGF-α/EGFR. We hypothesized that HGF/c-Met and TGF-α/EGFR would regulate innate immune responses to influenza A virus infection in human AECs. We found that recombinant human HGF (rhHGF) and rhTGF-α stimulated primary human AECs to secrete IL-8 and granulocyte macrophage colony-stimulating factor (GM-CSF) strongly and IL-6 and monocyte chemotactic protein 1 moderately. Influenza infection stimulated the secretion of IL-8 and GM-CSF by AECs plated on rat-tail collagen through EGFR activation likely by TGF-α released from AECs and through c-Met activated by HGF secreted from lung fibroblasts. HGF secretion by fibroblasts was stimulated by AEC production of prostaglandin E2 during influenza infection. We conclude that HGF/c-Met and TGF-α/EGFR signaling enhances the innate immune responses by human AECs during influenza infections.

scholarly journals Innate Immune Responses to Bacterial Ligands in the Peripheral Human Lung – Role of Alveolar Epithelial TLR Expression and Signalling

PLoS ONE ◽  
2011 ◽  
Vol 6 (7) ◽  
pp. e21827 ◽  
Author(s):  
Andrew J. Thorley ◽  
Davide Grandolfo ◽  
Eric Lim ◽  
Peter Goldstraw ◽  
Alan Young ◽  
...  
Keyword(s):  
Immune Responses ◽  
Human Lung ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Alveolar Epithelial

scholarly journals Complex Involvement of Interleukin-26 in Bacterial Lung Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Karlhans F. Che ◽  
Magnus Paulsson ◽  
Krzysztof Piersiala ◽  
Jakob Sax ◽  
Ibrahim Mboob ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Immune Responses ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Lung Infection ◽  
Innate Immune ◽  
Alveolar Epithelial Cells ◽  
Lower Airway ◽  
Innate Immune Responses ◽  
Human Lung Tissue

Pneumonia is a global cause of mortality, and this provides a strong incentive to improve the mechanistic understanding of innate immune responses in the lungs. Here, we characterized the involvement of the cytokine interleukin (IL)-26 in bacterial lung infection. We observed markedly increased concentrations of IL-26 in lower airway samples from patients with bacterial pneumonia and these correlated with blood neutrophil concentrations. Moreover, pathogen-associated molecular patterns (PAMPs) from both Gram-negative and -positive bacteria increased extracellular IL-26 concentrations in conditioned media from human models of alveolar epithelial cells, macrophages, and neutrophils in vitro. Stimulation with IL-26 inhibited the inherent release of neutrophil elastase and myeloperoxidase in unexposed neutrophils. This stimulation also inhibited the expression of activity makers in neutrophils exposed to Klebsiella pneumoniae. In addition, priming of human lung tissue ex vivo with exogenous IL-26 potentiated the endotoxin-induced increase in mRNA for other cytokines involved in the innate immune response, including the master Th17-regulator IL-23 and the archetype inhibitory cytokine IL-10. Finally, neutralization of endogenous IL-26 clearly increased the growth of Klebsiella pneumoniae in the macrophage culture. These findings suggest that IL-26 is involved in bacterial lung infection in a complex manner, by modulating critical aspects of innate immune responses locally and systemically in a seemingly purposeful manner and by contributing to the killing of bacteria in a way that resembles an antimicrobial peptide. Thus, IL-26 displays both diagnostic and therapeutic potential in pneumonia and deserves to be further evaluated in these respects.

scholarly journals The Roles of Two Clip Domain Serine Proteases in Innate Immune Responses of the Malaria VectorAnopheles gambiae

2005 ◽  
Vol 280 (48) ◽  
pp. 40161-40168 ◽  
Author(s):  
Jennifer Volz ◽  
Mike A. Osta ◽  
Fotis C. Kafatos ◽  
Hans-Michael Müller
Keyword(s):  
Immune Responses ◽  
Serine Proteases ◽  
Innate Immune ◽  
Innate Immune Responses

Oral Immune Activation by Disgust and Disease-Related Pictures

2015 ◽  
Vol 29 (3) ◽  
pp. 119-129 ◽  
Author(s):  
Richard J. Stevenson ◽  
Deborah Hodgson ◽  
Megan J. Oaten ◽  
Luba Sominsky ◽  
Mehmet Mahmut ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Innate Immune Response ◽  
Negative Control ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Immune Markers ◽  
Before And After ◽  
Secondary Analyses ◽  
Image Set

Abstract. Both disgust and disease-related images appear able to induce an innate immune response but it is unclear whether these effects are independent or rely upon a common shared factor (e.g., disgust or disease-related cognitions). In this study we directly compared these two inductions using specifically generated sets of images. One set was disease-related but evoked little disgust, while the other set was disgust evoking but with less disease-relatedness. These two image sets were then compared to a third set, a negative control condition. Using a wholly within-subject design, participants viewed one image set per week, and provided saliva samples, before and after each viewing occasion, which were later analyzed for innate immune markers. We found that both the disease related and disgust images, relative to the negative control images, were not able to generate an innate immune response. However, secondary analyses revealed innate immune responses in participants with greater propensity to feel disgust following exposure to disease-related and disgusting images. These findings suggest that disgust images relatively free of disease-related themes, and disease-related images relatively free of disgust may be suboptimal cues for generating an innate immune response. Not only may this explain why disgust propensity mediates these effects, it may also imply a common pathway.

Sign in / Sign up

Export Citation Format

Share Document