Rhinovirus and Innate Immune Function of Airway Epithelium
manal elzoheiry2020, Frontiers in Cellular and Infection Microbiology
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Abstract
Airway epithelial cells, which lines the respiratory mucosa is in direct contact with the environment. Airway epithelial cells are the primary target for rhinovirus and other inhaled pathogens. In response to rhinovirus infection, airway epithelial cells mount both pro-inflammatory responses and antiviral innate immune responses to clear the virus efficiently. Some of the antiviral responses include the expression of IFNs, endoplasmic reticulum stress induced unfolded protein response and autophagy. Airway epithelial cells also recruits other innate immune cells to establish antiviral state and resolve the inflammation in the lungs. In patients with chronic lung disease, these responses may be either defective or induced in excess leading to deficient clearing of virus and sustained inflammation. In this review, we will discuss the mechanisms underlying antiviral innate immunity and the dysregulation of some of these mechanisms in patients with chronic lung diseases.
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An Overview of Innate Immune Response to Human Rhinovirus Infection
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Human rhinoviruses (HRV) are mainly associated with catarrh or the common cold and quite possibly cause one of the most unavoidable diseases in human beings. Although the HRV infections of the upper respiratory tract are generally somewhat harmless, there is increasing proof that HRV pave the way for more hazardous infections, promote asthmatic intensifications, and lead to severe diseases in the lower respiratory tract. Respiratory tract epithelial cells are the essential targets for rhinovirus and other respiratory pathogens. In the presence of rhinovirus, respiratory tract epithelial cells mount both supportive of provocative reactions and antiviral natural invulnerable reactions to clear the infection effectively. A portion of antiviral reactions include the expression of interferons (IFNs) and endoplasmic reticulum stress-actuated unfolded protein reaction and autophagy. In patients with chronic (persistent) lung diseases, these reactions may be either imperfect or incited in overabundance prompting insufficient getting free from infection and supported aggravation. In this review, components hidden behind innate antiviral invulnerability and the dysregulation of a portion of these instruments will be examined in patients with chronic lung diseases.
Asthmatic bronchial epithelial cells have a deficient innate immune response to infection with rhinovirus
Journal of Experimental Medicine, 2005
Rhinoviruses are the major trigger of acute asthma exacerbations and asthmatic subjects are more susceptible to these infections. To investigate the underlying mechanisms of this increased susceptibility, we examined virus replication and innate responses to rhinovirus (RV)-16 infection of primary bronchial epithelial cells from asthmatic and healthy control subjects.
Increased Cytokine Response of Rhinovirus-infected Airway Epithelial Cells in Chronic Obstructive Pulmonary Disease
American Journal of Respiratory and Critical Care Medicine, 2010
Rationale: Airway inflammation is a central feature of chronic obstructive pulmonary disease (COPD). COPD exacerbations are often triggered by rhinovirus (RV) infection. Objectives: We hypothesized that airway epithelial cells from patients with COPD maintain a proinflammatory phenotype compared with control subjects, leading to greater RV responses. Methods: Cells were isolated from tracheobronchial tissues of 12 patients with COPD and 10 transplant donors. Eight patients with COPD had severe emphysema, three had mild to moderate emphysema, and one had no emphysema. All had moderate to severe airflow obstruction, and six met criteria for chronic bronchitis or had at least one exacerbation the previous year. Cells were grown at airliquid interface and infected with RV serotype 39. Cytokine and IFN expression was measured by ELISA. Selected genes involved in inflammation, oxidative stress, and proteolysis were assessed by focused gene array and real-time polymerase chain reaction. Measurements and Main Results: Compared with control subjects, cells from patients with COPD demonstrated increased mRNA expression of genes involved in oxidative stress and the response to viral infection, including NOX1, DUOXA2, MMP12, ICAM1, DDX58/RIG-I, STAT1, and STAT2. COPD cells showed elevated baseline and RVstimulated protein levels of IL-6, IL-8/CXCL8, and growth-related oncogene-a/CXCL1. COPD cells demonstrated increased viral titer and copy number after RV infection, despite increased IL-29/IFN-l1, IL-28A/IFN-l2, and IFN-inducible protein-10/CXCL10 protein levels. Finally, RV-infected COPD cultures showed increased mRNA expression of IL28A/IFNl2, IL29/IFNl1, IFIH1/MDA5, DDX58/RIG-I, DUOX1, DUOX2, IRF7, STAT1, and STAT2. Conclusions: Airway epithelial cells from patients with COPD show higher baseline levels of cytokine expression and increased susceptibility to RV infection, despite an increased IFN response.
Understanding the Immune and Inflammatory Response to Rhinoviruses: Recent Advances with Relevance to Asthma
Current Respiratory Medicine Reviews, 2016
Human rhinoviruses (HRVs) are responsible for most cases of the common cold. In healthy people, the consequences of HRV infections are usually minor. However, this innocuous virus can have serious consequences in certain individuals, with HRV infections linked to the onset of asthma in young children, and to potentially life threatening exacerbations in those with established asthma. Understanding the pathogenesis of HRV infections in asthma is thus a subject of much interest. This article reviews recent advances in our understanding of HRV-induced inflammatory pathways and immune responses, focussing on publications from the last 4 years. We outline new insights into the different types of HRVs, the cellular receptors they engage, and the transcriptional pathways that are engaged as a prelude to interferon synthesis. The importance of cross-talk between the innate immune response to HRV infections and cytokines produced during allergic inflammation is emphasised, with researchers continuing to document both altered anti-viral interferon production and immune dysregulation in asthma. Better definition of the mechanisms by which HRV infections induces lower airway inflammation is an important foundation on which to develop novel therapies that target HRV and/or the immunopathology that it induces.
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Proceedings of the …, 2005
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Airway inflammation and illness severity in response to experimental rhinovirus infection in asthma
CHEST Journal, 2014
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Allergy, asthma & immunology research, 2018
In order to gain an insight into determinants of reported variability in immune responses to respiratory viruses in human bronchial epithelial cells (HBECs) from asthmatics, the responses of HBEC to viral infections were evaluated in HBECs from phenotypically heterogeneous groups of asthmatics and in healthy controls. HBECs were obtained during bronchoscopy from 10 patients with asthma (6 atopic and 4 non-atopic) and from healthy controls (n=9) and grown as undifferentiated cultures. HBECs were infected with parainfluenza virus (PIV)-3 (MOI 0.1) and rhinovirus (RV)-1B (MOI 0.1), or treated with medium alone. The cell supernatants were harvested at 8, 24, and 48 hours. IFN-α, CXCL10 (IP-10), and RANTES (CCL5) were analyzed by using Cytometric Bead Array (CBA), and interferon (IFN)-β and IFN-λ1 by ELISA. Gene expression of IFNs, chemokines, and IFN-regulatory factors (IRF-3 and IRF-7) was determined by using quantitative PCR. PIV3 and RV1B infections increased IFN-λ1 mRNA expression i...
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Elucidating the Interaction of CF Airway Epithelial Cells and Rhinovirus: Using the Host-Pathogen Relationship to Identify Future Therapeutic Strategies
Frontiers in Pharmacology, 2018
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American Journal of Respiratory Cell and Molecular Biology, 2006
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