NOX4 Is A Potential Regulator Of Innate Immune Responses In Alveolar Epithelial Cells During Herpesvirus Infection

2012 ◽  
Author(s):  
Tracy R. Luckhardt ◽  
Lanfang Wang ◽  
Guangjie Cheng ◽  
Louise Hecker ◽  
Victor J. Thannickal
Keyword(s):  
Epithelial Cells ◽  
Immune Responses ◽  
Innate Immune ◽  
Alveolar Epithelial Cells ◽  
Innate Immune Responses ◽  
Herpesvirus Infection ◽  
Alveolar Epithelial

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 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 Herpes Simplex Virus 1 Infection of Neuronal and Non-Neuronal Cells Elicits Specific Innate Immune Responses and Immune Evasion Mechanisms

2021 ◽  
Vol 12 ◽  
Author(s):  
Amanda L. Verzosa ◽  
Lea A. McGeever ◽  
Shun-Je Bhark ◽  
Tracie Delgado ◽  
Nicole Salazar ◽  
...  
Keyword(s):  
Herpes Simplex ◽  
Epithelial Cells ◽  
Immune Responses ◽  
Host Cell ◽  
Signaling Pathways ◽  
Sensory Neurons ◽  
Immune Evasion ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Hsv 1

Alphaherpesviruses (α-HV) are a large family of double-stranded DNA viruses which cause many human and animal diseases. There are three human α-HVs: Herpes Simplex Viruses (HSV-1 and HSV-2) and Varicella Zoster Virus (VZV). All α-HV have evolved multiple strategies to suppress or exploit host cell innate immune signaling pathways to aid in their infections. All α-HVs initially infect epithelial cells (primary site of infection), and later spread to infect innervating sensory neurons. As with all herpesviruses, α-HVs have both a lytic (productive) and latent (dormant) stage of infection. During the lytic stage, the virus rapidly replicates in epithelial cells before it is cleared by the immune system. In contrast, latent infection in host neurons is a life-long infection. Upon infection of mucosal epithelial cells, herpesviruses immediately employ a variety of cellular mechanisms to evade host detection during active replication. Next, infectious viral progeny bud from infected cells and fuse to neuronal axonal terminals. Here, the nucleocapsid is transported via sensory neuron axons to the ganglion cell body, where latency is established until viral reactivation. This review will primarily focus on how HSV-1 induces various innate immune responses, including host cell recognition of viral constituents by pattern-recognition receptors (PRRs), induction of IFN-mediated immune responses involving toll-like receptor (TLR) signaling pathways, and cyclic GMP‐AMP synthase stimulator of interferon genes (cGAS-STING). This review focuses on these pathways along with other mechanisms including autophagy and the complement system. We will summarize and discuss recent evidence which has revealed how HSV-1 is able to manipulate and evade host antiviral innate immune responses both in neuronal (sensory neurons of the trigeminal ganglia) and non-neuronal (epithelial) cells. Understanding the innate immune response mechanisms triggered by HSV-1 infection, and the mechanisms of innate immune evasion, will impact the development of future therapeutic treatments.

scholarly journals Host Mucin Is Exploited by Pseudomonas aeruginosa To Provide Monosaccharides Required for a Successful Infection

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Casandra L. Hoffman ◽  
Jonathan Lalsiamthara ◽  
Alejandro Aballay
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Caenorhabditis Elegans ◽  
Epithelial Cells ◽  
Human Lung ◽  
Innate Immune ◽  
Alveolar Epithelial Cells ◽  
Content Type ◽  
Alveolar Epithelial ◽  
Successful Infection ◽  
Wide Range

ABSTRACT One of the primary functions of the mucosal barrier, found lining epithelial cells, is to serve as a first-line of defense against microbial pathogens. The major structural components of mucus are heavily glycosylated proteins called mucins. Mucins are key components of the innate immune system as they aid in the clearance of pathogens and can decrease pathogen virulence. It has also been recently reported that individual mucins and derived glycans can attenuate the virulence of the human pathogen Pseudomonas aeruginosa. Here, we show data indicating that mucins not only play a role in host defense but that they can also be subverted by P. aeruginosa to cause disease. We found that the mucin MUL-1 and mucin-derived monosaccharides N-acetyl-galactosamine and N-acetylglucosamine are required for P. aeruginosa killing of Caenorhabditis elegans. We also found that the defective adhesion of P. aeruginosa to human lung alveolar epithelial cells, deficient in the mucin MUC1, can be reversed by the addition of individual monosaccharides. The monosaccharides identified in this study are found in a wide range of organisms where they act as host factors required for bacterial pathogenesis. While mucins in C. elegans lack sialic acid caps, which makes their monosaccharides readily available, they are capped in other species. Pathogens such as P. aeruginosa that lack sialidases may rely on enzymes from other bacteria to utilize mucin-derived monosaccharides. IMPORTANCE One of the first lines of defense present at mucosal epithelial tissues is mucus, which is a highly viscous material formed by mucin glycoproteins. Mucins serve various functions, but importantly they aid in the clearance of pathogens and debris from epithelial barriers and serve as innate immune factors. In this study, we describe a requirement of host monosaccharides, likely derived from host mucins, for the ability of Pseudomonas aeruginosa to colonize the intestine and ultimately cause death in Caenorhabditis elegans. We also demonstrate that monosaccharides alter the ability of bacteria to bind to both Caenorhabditis elegans intestinal cells and human lung alveolar epithelial cells, suggesting that there are conserved mechanisms underlying host-pathogen interactions in a range of organisms. By gaining a better understanding of pathogen-mucin interactions, we can develop better approaches to protect against pathogen infection.

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