Su-Ling Loo - Academia.edu (original) (raw)

Papers by Su-Ling Loo

Research paper thumbnail of Airway Epithelial Cells from Patients with Asthma and COPD Exhibit Improved Resistance to Rhinovirus Infection Following Treatment with TLR2 Immune Modulators

Research paper thumbnail of Antiviral immunity is impaired in COPD patients with frequent exacerbations

American Journal of Physiology-lung Cellular and Molecular Physiology, Dec 1, 2019

Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) sub... more Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) subgroup requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD. We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virusassociated exacerbations. In vitro immune responses to rhinovirus infection in differentiated primary bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators (Ն2 exacerbations in the preceding year) or infrequent exacerbators (Ͻ2 exacerbations in the preceding year) with comparisons made between these groups. Frequent exacerbators had reduced sputum cell mRNA expression of the antiviral immune mediators type I and III interferons and reduced interferon-stimulated gene (ISG) expression when clinically stable and during virus-associated exacerbation. A role for epithelial cellintrinsic innate immune dysregulation was identified: induction of interferons and ISGs during in vitro rhinovirus (RV) infection was also impaired in differentiated BECs from frequent exacerbators. Frequent exacerbators additionally had increased sputum bacterial loads at 2 wk following virus-associated exacerbation onset. These data implicate deficient airway innate immunity involving epithelial cells in the increased propensity to exacerbations observed in some patients with COPD. Therapeutic approaches to boost innate antimicrobial immunity in the lung could be a viable strategy for prevention and treatment of frequent exacerbations. COPD; innate immunity; viral infection

Research paper thumbnail of Anti-microbial immunity is impaired in COPD patients with frequent exacerbations

Research paper thumbnail of A Mouse Upper Respiratory Tract Coronavirus Infection Model with OC43 Defines Toll-Like Receptor 2/6 Mediated Innate Immune Protection

Research paper thumbnail of IL-25 blockade augments antiviral immunity during respiratory virus infection

Communications Biology

IL-25 is implicated in the pathogenesis of viral asthma exacerbations. However, the effect of IL-... more IL-25 is implicated in the pathogenesis of viral asthma exacerbations. However, the effect of IL-25 on antiviral immunity has yet to be elucidated. We observed abundant expression and colocalization of IL-25 and IL-25 receptor at the apical surface of uninfected airway epithelial cells and rhinovirus infection increased IL-25 expression. Analysis of immune transcriptome of rhinovirus-infected differentiated asthmatic bronchial epithelial cells (BECs) treated with an anti-IL-25 monoclonal antibody (LNR125) revealed a re-calibrated response defined by increased type I/III IFN and reduced expression of type-2 immune genes CCL26, IL1RL1 and IL-25 receptor. LNR125 treatment also increased type I/III IFN expression by coronavirus infected BECs. Exogenous IL-25 treatment increased viral load with suppressed innate immunity. In vivo LNR125 treatment reduced IL-25/type 2 cytokine expression and increased IFN-β expression and reduced lung viral load. We define a new immune-regulatory role for...

Research paper thumbnail of IL-25 Inhibits Airway Anti-Viral Immunity and Promotes Virus Exacerbation of Allergic Airways Disease

A28. THE HOST DELIVERS, May 1, 2022

Research paper thumbnail of TLR2/6 Agonist Treatment Enhances Antiviral Innate Immune Responses in a Novel Mouse Coronavirus Respiratory Infection Model

A28. THE HOST DELIVERS, May 1, 2022

Research paper thumbnail of Rhinovirus diversity and virulence factors

Rhinovirus Infections, 2019

Abstract The rhinovirus (RV) genus is highly diverse, consisting of three species and more than 1... more Abstract The rhinovirus (RV) genus is highly diverse, consisting of three species and more than 167 subtypes, utilizing three different receptors for cell entry. This diversity has been an obstacle to the development of effective cross-reactive antiviral treatments or vaccine strategies. Accumulating research suggests a possible association of virus species/subtypes with illness severity presenting the possibility for antiviral approaches targeting specific subtypes instead of all RVs. To facilitate such an approach, identification of the underlying molecular mechanism and the viral factor/s that mediate disease is required. Recent literature shows a clear species/subtype associated divergence in the host cell directed activity of RV proteases. Whether these differences correlate with the subtype-specific differences in illness severity remains to be confirmed. In this chapter, we bring together current knowledge of the association of RV species/subtypes with illness and explore the possible role of RV proteases as the main virulence factors associated with illness severity.

Research paper thumbnail of TLR2-mediated innate immune priming boosts lung anti-viral immunity

European Respiratory Journal, 2020

BackgroundWe assessed whether Toll-like receptor (TLR)2 activation boosts the innate immune respo... more BackgroundWe assessed whether Toll-like receptor (TLR)2 activation boosts the innate immune response to rhinovirus infection, as a treatment strategy for virus-induced respiratory diseases.MethodsWe employed treatment with a novel TLR2 agonist (INNA-X) prior to rhinovirus infection in mice, and INNA-X treatment in differentiated human bronchial epithelial cells derived from asthmatic-donors. We assessed viral load, immune cell recruitment, cytokines, type I and III interferon (IFN) production, as well as the lung tissue and epithelial cell immune transcriptome.ResultsWe show,in vivo, that a single INNA-X treatment induced innate immune priming characterised by low-level IFN-λ, Fas ligand, chemokine expression and airway lymphocyte recruitment. Treatment 7 days before infection significantly reduced lung viral load, increased IFN-β/λ expression and inhibited neutrophilic inflammation. Corticosteroid treatment enhanced the anti-inflammatory effects of INNA-X. Treatment 1 day before in...

Research paper thumbnail of Inhaled corticosteroids downregulate the SARS-CoV-2 receptor ACE2 in COPD through suppression of type I interferon

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is a new rapidly spreading infectious di... more Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is a new rapidly spreading infectious disease. Early reports of hospitalised COVID-19 cases have shown relatively low frequency of chronic lung diseases such as chronic obstructive pulmonary disease (COPD) but increased risk of adverse outcome. The mechanisms of altered susceptibility to viral acquisition and/or severe disease in at-risk groups are poorly understood. Inhaled corticosteroids (ICS) are widely used in the treatment of COPD but the extent to which these therapies protect or expose patients with a COPD to risk of increased COVID-19 severity is unknown. Here, using a combination of human and animalin vitroandin vivodisease models, we show that ICS administration attenuates pulmonary expression of the SARS-CoV-2 viral entry receptor angiotensin-converting enzyme (ACE)-2. This effect was mechanistically driven by suppression of type I interferon as exogenous interferon-β reversed ACE2 downregulation by ICS. Mice defic...

Research paper thumbnail of Antiviral immunity is impaired in COPD patients with frequent exacerbations

American Journal of Physiology-Lung Cellular and Molecular Physiology, 2019

Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) sub... more Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) subgroup requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD. We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virus-associated exacerbations. In vitro immune responses to rhinovirus infection in differentiated primary bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators (≥2 exacerbations in the preceding year) or infrequent exacerbators (<2 exacerbations in the preceding year) with comparisons made between these groups. Frequent exacerbators had reduced sputum cell mRNA expression of the antiviral immune mediators type I and III interferons and reduced interferon-stimulated gene (ISG) expression when c...

Research paper thumbnail of Airway Epithelial Cells from Patients with Asthma and COPD Exhibit Improved Resistance to Rhinovirus Infection Following Treatment with TLR2 Immune Modulators

D21. HOST RESPONSE TO LUNG INFECTIONS, 2019

Research paper thumbnail of Anti-microbial immunity is impaired in COPD patients with frequent exacerbations

Background: Patients with frequent exacerbations represent a chronic obstructive pulmonary diseas... more Background: Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) sub-group requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD. Methods: We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virus-associated exacerbations. Ex vivo immune responses to rhinovirus infection in differentiated bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators (>2 exacerbations in the preceding year) or infrequent exacerbators (<2 exacerbations in the preceding year) with comparisons made between these groups. Results: Frequent exacerbators had reduced sputum cell mRNA expression of the anti-viral immune mediators type I and III interferons and reduced interferon-stimulated ge...

Research paper thumbnail of Corticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations

Nature communications, Jun 8, 2018

Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary dis... more Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms. Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections. Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations. Exogenous interferon-β reverses these effects. FP suppression of interferon may occur through inhibition of TLR3- and RIG-I virus-sensing pathways. Mice deficient in the type I interferon-α/β receptor (IFNAR1) have suppressed antimicrobial peptide and enhanced mucin responses to rhinovirus infection. This study identifies type I interferon as a central regulator of antibacterial immu...

Research paper thumbnail of Airway Epithelial and Early Innate Immune Responses to Virus Infections

Human Respiratory Viral Infections, 2014

Research paper thumbnail of Human coronaviruses 229E and OC43 replicate and induce distinct antiviral responses in differentiated primary human bronchial epithelial cells

American Journal of Physiology-Lung Cellular and Molecular Physiology, 2020

The recurrent emergence of novel, pathogenic coronaviruses (CoVs) severe acute respiratory syndro... more The recurrent emergence of novel, pathogenic coronaviruses (CoVs) severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1; 2002), Middle East respiratory syndrome (MERS)-CoV (2012), and most recently SARS-CoV-2 (2019) has highlighted the need for physiologically informative airway epithelial cell infection models for studying immunity to CoVs and development of antiviral therapies. To address this, we developed an in vitro infection model for two human coronaviruses; alphacoronavirus 229E-CoV (229E) and betacoronavirus OC43-CoV (OC43) in differentiated primary human bronchial epithelial cells (pBECs). Primary BECs from healthy subjects were grown at air-liquid interface (ALI) and infected with 229E or OC43, and replication kinetics and time-course expression of innate immune mediators were assessed. OC43 and 229E-CoVs replicated in differentiated pBECs but displayed distinct replication kinetics: 229E replicated rapidly with viral load peaking at 24 h postinfection, while OC43 r...

Research paper thumbnail of Ground zero—the airway epithelium

Rhinovirus Infections

Abstract The airway epithelium remains the first line of defense against insult, since it lies at... more Abstract The airway epithelium remains the first line of defense against insult, since it lies at the interface between the external environment and the internal milieu. Although thought to play a simple barrier role in this capacity, it has now been recognized to respond to the external environment and infectious stimuli via mediator release that direct signals with immune and mesenchymal cells. Specifically, in response to viral has developed a multifaceted approach to trapping and eliminating virus. A compromised epithelial barrier in diseases such as asthma, chronic obstructive pulmonary disease, or cystic fibrosis dramatically increases the risk of pathogenic infection. During infection, airway epithelial cells become the primary site of replication for respiratory viruses such as rhinovirus (RV) and initiate the hosts’ immune responses. This chapter will discuss the structure of the airway highlighting the now broad number of cell types that comprise it. It will discuss these in the context of health and inflammatory respiratory disease as well as their role in facilitating viral infection. In addition, this chapter will summarize the primary roles of the airway, including its mucociliary, barrier, and reparative functions in these settings. We will examine the interaction between the airway epithelium and RV, which promotes viral attachment, subsequent entry, and replication, and elaborate on the innate response of the airway to viral infection. Finally, we review the literature on interventional studies conducted to combat RV infection.

Research paper thumbnail of Recent advances in understanding and managing asthma

Research paper thumbnail of Airway Epithelial and Early Innate Immune Responses to Virus Infections

Human Respiratory Viral Infections, 2014

Research paper thumbnail of Airway Epithelial Cells from Patients with Asthma and COPD Exhibit Improved Resistance to Rhinovirus Infection Following Treatment with TLR2 Immune Modulators

Research paper thumbnail of Antiviral immunity is impaired in COPD patients with frequent exacerbations

American Journal of Physiology-lung Cellular and Molecular Physiology, Dec 1, 2019

Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) sub... more Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) subgroup requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD. We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virusassociated exacerbations. In vitro immune responses to rhinovirus infection in differentiated primary bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators (Ն2 exacerbations in the preceding year) or infrequent exacerbators (Ͻ2 exacerbations in the preceding year) with comparisons made between these groups. Frequent exacerbators had reduced sputum cell mRNA expression of the antiviral immune mediators type I and III interferons and reduced interferon-stimulated gene (ISG) expression when clinically stable and during virus-associated exacerbation. A role for epithelial cellintrinsic innate immune dysregulation was identified: induction of interferons and ISGs during in vitro rhinovirus (RV) infection was also impaired in differentiated BECs from frequent exacerbators. Frequent exacerbators additionally had increased sputum bacterial loads at 2 wk following virus-associated exacerbation onset. These data implicate deficient airway innate immunity involving epithelial cells in the increased propensity to exacerbations observed in some patients with COPD. Therapeutic approaches to boost innate antimicrobial immunity in the lung could be a viable strategy for prevention and treatment of frequent exacerbations. COPD; innate immunity; viral infection

Research paper thumbnail of Anti-microbial immunity is impaired in COPD patients with frequent exacerbations

Research paper thumbnail of A Mouse Upper Respiratory Tract Coronavirus Infection Model with OC43 Defines Toll-Like Receptor 2/6 Mediated Innate Immune Protection

Research paper thumbnail of IL-25 blockade augments antiviral immunity during respiratory virus infection

Communications Biology

IL-25 is implicated in the pathogenesis of viral asthma exacerbations. However, the effect of IL-... more IL-25 is implicated in the pathogenesis of viral asthma exacerbations. However, the effect of IL-25 on antiviral immunity has yet to be elucidated. We observed abundant expression and colocalization of IL-25 and IL-25 receptor at the apical surface of uninfected airway epithelial cells and rhinovirus infection increased IL-25 expression. Analysis of immune transcriptome of rhinovirus-infected differentiated asthmatic bronchial epithelial cells (BECs) treated with an anti-IL-25 monoclonal antibody (LNR125) revealed a re-calibrated response defined by increased type I/III IFN and reduced expression of type-2 immune genes CCL26, IL1RL1 and IL-25 receptor. LNR125 treatment also increased type I/III IFN expression by coronavirus infected BECs. Exogenous IL-25 treatment increased viral load with suppressed innate immunity. In vivo LNR125 treatment reduced IL-25/type 2 cytokine expression and increased IFN-β expression and reduced lung viral load. We define a new immune-regulatory role for...

Research paper thumbnail of IL-25 Inhibits Airway Anti-Viral Immunity and Promotes Virus Exacerbation of Allergic Airways Disease

A28. THE HOST DELIVERS, May 1, 2022

Research paper thumbnail of TLR2/6 Agonist Treatment Enhances Antiviral Innate Immune Responses in a Novel Mouse Coronavirus Respiratory Infection Model

A28. THE HOST DELIVERS, May 1, 2022

Research paper thumbnail of Rhinovirus diversity and virulence factors

Rhinovirus Infections, 2019

Abstract The rhinovirus (RV) genus is highly diverse, consisting of three species and more than 1... more Abstract The rhinovirus (RV) genus is highly diverse, consisting of three species and more than 167 subtypes, utilizing three different receptors for cell entry. This diversity has been an obstacle to the development of effective cross-reactive antiviral treatments or vaccine strategies. Accumulating research suggests a possible association of virus species/subtypes with illness severity presenting the possibility for antiviral approaches targeting specific subtypes instead of all RVs. To facilitate such an approach, identification of the underlying molecular mechanism and the viral factor/s that mediate disease is required. Recent literature shows a clear species/subtype associated divergence in the host cell directed activity of RV proteases. Whether these differences correlate with the subtype-specific differences in illness severity remains to be confirmed. In this chapter, we bring together current knowledge of the association of RV species/subtypes with illness and explore the possible role of RV proteases as the main virulence factors associated with illness severity.

Research paper thumbnail of TLR2-mediated innate immune priming boosts lung anti-viral immunity

European Respiratory Journal, 2020

BackgroundWe assessed whether Toll-like receptor (TLR)2 activation boosts the innate immune respo... more BackgroundWe assessed whether Toll-like receptor (TLR)2 activation boosts the innate immune response to rhinovirus infection, as a treatment strategy for virus-induced respiratory diseases.MethodsWe employed treatment with a novel TLR2 agonist (INNA-X) prior to rhinovirus infection in mice, and INNA-X treatment in differentiated human bronchial epithelial cells derived from asthmatic-donors. We assessed viral load, immune cell recruitment, cytokines, type I and III interferon (IFN) production, as well as the lung tissue and epithelial cell immune transcriptome.ResultsWe show,in vivo, that a single INNA-X treatment induced innate immune priming characterised by low-level IFN-λ, Fas ligand, chemokine expression and airway lymphocyte recruitment. Treatment 7 days before infection significantly reduced lung viral load, increased IFN-β/λ expression and inhibited neutrophilic inflammation. Corticosteroid treatment enhanced the anti-inflammatory effects of INNA-X. Treatment 1 day before in...

Research paper thumbnail of Inhaled corticosteroids downregulate the SARS-CoV-2 receptor ACE2 in COPD through suppression of type I interferon

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is a new rapidly spreading infectious di... more Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 is a new rapidly spreading infectious disease. Early reports of hospitalised COVID-19 cases have shown relatively low frequency of chronic lung diseases such as chronic obstructive pulmonary disease (COPD) but increased risk of adverse outcome. The mechanisms of altered susceptibility to viral acquisition and/or severe disease in at-risk groups are poorly understood. Inhaled corticosteroids (ICS) are widely used in the treatment of COPD but the extent to which these therapies protect or expose patients with a COPD to risk of increased COVID-19 severity is unknown. Here, using a combination of human and animalin vitroandin vivodisease models, we show that ICS administration attenuates pulmonary expression of the SARS-CoV-2 viral entry receptor angiotensin-converting enzyme (ACE)-2. This effect was mechanistically driven by suppression of type I interferon as exogenous interferon-β reversed ACE2 downregulation by ICS. Mice defic...

Research paper thumbnail of Antiviral immunity is impaired in COPD patients with frequent exacerbations

American Journal of Physiology-Lung Cellular and Molecular Physiology, 2019

Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) sub... more Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) subgroup requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD. We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virus-associated exacerbations. In vitro immune responses to rhinovirus infection in differentiated primary bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators (≥2 exacerbations in the preceding year) or infrequent exacerbators (<2 exacerbations in the preceding year) with comparisons made between these groups. Frequent exacerbators had reduced sputum cell mRNA expression of the antiviral immune mediators type I and III interferons and reduced interferon-stimulated gene (ISG) expression when c...

Research paper thumbnail of Airway Epithelial Cells from Patients with Asthma and COPD Exhibit Improved Resistance to Rhinovirus Infection Following Treatment with TLR2 Immune Modulators

D21. HOST RESPONSE TO LUNG INFECTIONS, 2019

Research paper thumbnail of Anti-microbial immunity is impaired in COPD patients with frequent exacerbations

Background: Patients with frequent exacerbations represent a chronic obstructive pulmonary diseas... more Background: Patients with frequent exacerbations represent a chronic obstructive pulmonary disease (COPD) sub-group requiring better treatment options. The aim of this study was to determine the innate immune mechanisms that underlie susceptibility to frequent exacerbations in COPD. Methods: We measured sputum expression of immune mediators and bacterial loads in samples from patients with COPD at stable state and during virus-associated exacerbations. Ex vivo immune responses to rhinovirus infection in differentiated bronchial epithelial cells (BECs) sampled from patients with COPD were additionally evaluated. Patients were stratified as frequent exacerbators (>2 exacerbations in the preceding year) or infrequent exacerbators (<2 exacerbations in the preceding year) with comparisons made between these groups. Results: Frequent exacerbators had reduced sputum cell mRNA expression of the anti-viral immune mediators type I and III interferons and reduced interferon-stimulated ge...

Research paper thumbnail of Corticosteroid suppression of antiviral immunity increases bacterial loads and mucus production in COPD exacerbations

Nature communications, Jun 8, 2018

Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary dis... more Inhaled corticosteroids (ICS) have limited efficacy in reducing chronic obstructive pulmonary disease (COPD) exacerbations and increase pneumonia risk, through unknown mechanisms. Rhinoviruses precipitate most exacerbations and increase susceptibility to secondary bacterial infections. Here, we show that the ICS fluticasone propionate (FP) impairs innate and acquired antiviral immune responses leading to delayed virus clearance and previously unrecognised adverse effects of enhanced mucus, impaired antimicrobial peptide secretion and increased pulmonary bacterial load during virus-induced exacerbations. Exogenous interferon-β reverses these effects. FP suppression of interferon may occur through inhibition of TLR3- and RIG-I virus-sensing pathways. Mice deficient in the type I interferon-α/β receptor (IFNAR1) have suppressed antimicrobial peptide and enhanced mucin responses to rhinovirus infection. This study identifies type I interferon as a central regulator of antibacterial immu...

Research paper thumbnail of Airway Epithelial and Early Innate Immune Responses to Virus Infections

Human Respiratory Viral Infections, 2014

Research paper thumbnail of Human coronaviruses 229E and OC43 replicate and induce distinct antiviral responses in differentiated primary human bronchial epithelial cells

American Journal of Physiology-Lung Cellular and Molecular Physiology, 2020

The recurrent emergence of novel, pathogenic coronaviruses (CoVs) severe acute respiratory syndro... more The recurrent emergence of novel, pathogenic coronaviruses (CoVs) severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1; 2002), Middle East respiratory syndrome (MERS)-CoV (2012), and most recently SARS-CoV-2 (2019) has highlighted the need for physiologically informative airway epithelial cell infection models for studying immunity to CoVs and development of antiviral therapies. To address this, we developed an in vitro infection model for two human coronaviruses; alphacoronavirus 229E-CoV (229E) and betacoronavirus OC43-CoV (OC43) in differentiated primary human bronchial epithelial cells (pBECs). Primary BECs from healthy subjects were grown at air-liquid interface (ALI) and infected with 229E or OC43, and replication kinetics and time-course expression of innate immune mediators were assessed. OC43 and 229E-CoVs replicated in differentiated pBECs but displayed distinct replication kinetics: 229E replicated rapidly with viral load peaking at 24 h postinfection, while OC43 r...

Research paper thumbnail of Ground zero—the airway epithelium

Rhinovirus Infections

Abstract The airway epithelium remains the first line of defense against insult, since it lies at... more Abstract The airway epithelium remains the first line of defense against insult, since it lies at the interface between the external environment and the internal milieu. Although thought to play a simple barrier role in this capacity, it has now been recognized to respond to the external environment and infectious stimuli via mediator release that direct signals with immune and mesenchymal cells. Specifically, in response to viral has developed a multifaceted approach to trapping and eliminating virus. A compromised epithelial barrier in diseases such as asthma, chronic obstructive pulmonary disease, or cystic fibrosis dramatically increases the risk of pathogenic infection. During infection, airway epithelial cells become the primary site of replication for respiratory viruses such as rhinovirus (RV) and initiate the hosts’ immune responses. This chapter will discuss the structure of the airway highlighting the now broad number of cell types that comprise it. It will discuss these in the context of health and inflammatory respiratory disease as well as their role in facilitating viral infection. In addition, this chapter will summarize the primary roles of the airway, including its mucociliary, barrier, and reparative functions in these settings. We will examine the interaction between the airway epithelium and RV, which promotes viral attachment, subsequent entry, and replication, and elaborate on the innate response of the airway to viral infection. Finally, we review the literature on interventional studies conducted to combat RV infection.

Research paper thumbnail of Recent advances in understanding and managing asthma

Research paper thumbnail of Airway Epithelial and Early Innate Immune Responses to Virus Infections

Human Respiratory Viral Infections, 2014