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Viral asthma challenge model

Aran Singanayagam, Sebastian L Johnston
Inhaled β2-adrenoceptor agonists are a mainstay of therapy for airways diseases and are almost universally prescribed for patients with asthma or chronic obstructive pulmonary disease (COPD). Very few studies have evaluated the efficacy of these commonly used therapies during acute disease exacerbations which are frequently triggered by viral infection. In this edition of Clinical Science, Donovan et al. assess the ex vivo effects of the most commonly used short-acting β2-agonist salbutamol on small airway reactivity using precision cut lung slices (PCLS) from a mouse model of virus-induced exacerbation of COPD...
May 1, 2016: Clinical Science (1979-)
Thi Hiep Nguyen, Steven Maltby, Jodie L Simpson, Fiona Eyers, Katherine J Baines, Peter G Gibson, Paul S Foster, Ming Yang
Viral respiratory infections trigger severe exacerbations of asthma, worsen disease symptoms, and impair lung function. To investigate the mechanisms underlying viral exacerbation, we established a mouse model of respiratory syncytial virus (RSV)-induced exacerbation after allergen sensitization and challenge. RSV infection of OVA-sensitized/challenged BALB/c mice resulted in significantly increased airway hyperresponsiveness (AHR) and macrophage and neutrophil lung infiltration. Exacerbation was accompanied by increased levels of inflammatory cytokines (including TNF-α, MCP-1, and keratinocyte-derived protein chemokine [KC]) compared with uninfected OVA-treated mice or OVA-treated mice exposed to UV-inactivated RSV...
May 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Irma Mahmutovic Persson, Hamid Akbarshahi, Mandy Menzel, Angelica Brandelius, Lena Uller
BACKGROUND: Exacerbations of asthma caused by respiratory viral infections are serious conditions in need of novel treatment. To this end animal models of asthma exacerbations are warranted. We have shown that dsRNA challenges or rhinoviral infection produce exacerbation effects in mice with ovalbumin (OVA)-induced allergic asthma. However, house dust mite (HDM) is a more human asthma-relevant allergen than OVA. We thus hypothesised that dsRNA challenges in mice with HDM-induced experimental asthma would produce important translational features of asthma exacerbations...
2016: Journal of Translational Medicine
Yoichi Furuya, Andrea K M Furuya, Sean Roberts, Alan M Sanfilippo, Sharon L Salmon, Dennis W Metzger
Asthma is believed to be a risk factor for influenza infection, however little experimental evidence exists to directly demonstrate the impact of asthma on susceptibility to influenza infection. Using a mouse model, we now report that asthmatic mice are actually significantly more resistant to a lethal influenza virus challenge. Notably, the observed increased resistance was not attributable to enhanced viral clearance, but instead, was due to reduced lung inflammation. Asthmatic mice exhibited a significantly reduced cytokine storm, as well as reduced total protein levels and cytotoxicity in the airways, indicators of decreased tissue injury...
September 2015: PLoS Pathogens
Sara Saturni, Marco Contoli, Antonio Spanevello, Alberto Papi
Respiratory infections are one of the main health problems worldwide. They are a challenging field of study due to an intricate relationship between the pathogenicity of microbes and the host's defenses. To better understand mechanisms of respiratory infections, different models have been developed. A model is the reproduction of a disease in a system that mimics human pathophysiology. For this reason, the best models should closely resemble real-life conditions. Thus, the human model is the best. However, human models of respiratory infections have some disadvantages that limit their role...
November 2015: Allergy, Asthma & Immunology Research
Jorge De Alba, Raquel Otal, Elena Calama, Anna Domenech, Neus Prats, Neil Gozzard, Montserrat Miralpeix
RNA viruses are a major cause of respiratory infections and are known to exacerbate asthma and other respiratory diseases. Our aim was to test the ability of poly(I:C) (polyinosinic:polycytidylic acid), a viral surrogate, to elicit exacerbation in a model of severe asthma driven by HDM (house dust mite) in FCA (Freund's complete adjuvant). Poly(I:C) was administered intranasally around the HDM challenge in FCA-HDM-sensitized animals. Changes in AHR (airway hyperresponsiveness), BALF (bronchoalveolar lavage fluid) inflammatory infiltrate, HDM-specific immunoglobulins and cytokine/chemokine release were evaluated at different points after the challenge...
December 2015: Clinical Science (1979-)
Roxane Tussiwand, Bart Everts, Gary E Grajales-Reyes, Nicole M Kretzer, Arifumi Iwata, Juhi Bagaitkar, Xiaodi Wu, Rachel Wong, David A Anderson, Theresa L Murphy, Edward J Pearce, Kenneth M Murphy
The two major lineages of classical dendritic cells (cDCs) express and require either IRF8 or IRF4 transcription factors for their development and function. IRF8-dependent cDCs promote anti-viral and T-helper 1 (Th1) cell responses, whereas IRF4-expressing cDCs have been implicated in controlling both Th2 and Th17 cell responses. Here, we have provided evidence that Kruppel-like factor 4 (Klf4) is required in IRF4-expressing cDCs to promote Th2, but not Th17, cell responses in vivo. Conditional Klf4 deletion within cDCs impaired Th2 cell responses during Schistosoma mansoni infection, Schistosoma egg antigen (SEA) immunization, and house dust mite (HDM) challenge without affecting cytotoxic T lymphocyte (CTL), Th1 cell, or Th17 cell responses to herpes simplex virus, Toxoplasma gondii, and Citrobacter rodentium infections...
May 19, 2015: Immunity
Amanda R Lever, Hyoungshin Park, Thomas J Mulhern, George R Jackson, James C Comolli, Jeffrey T Borenstein, Patrick J Hayden, Rachelle Prantil-Baun
Respiratory viruses invade the upper airway of the lung, triggering a potent immune response that often exacerbates preexisting conditions such as asthma and COPD. Poly(I:C) is a synthetic analog of viral dsRNA that induces the characteristic inflammatory response associated with viral infection, such as loss of epithelial integrity, and increased production of mucus and inflammatory cytokines. Here, we explore the mechanistic responses to poly(I:C) in a well-defined primary normal human bronchial epithelial (NHBE) model that recapitulates in vivo functions and responses...
April 2015: Physiological Reports
Jianwu Bai, Steven L Smock, George R Jackson, Kenzie D MacIsaac, Yongsheng Huang, Courtney Mankus, Jonathan Oldach, Brian Roberts, Yu-Lu Ma, Joel A Klappenbach, Michael A Crackower, Stephen E Alves, Patrick J Hayden
OBJECTIVES: Human airway epithelial cells are the principal target of human rhinovirus (HRV), a common cold pathogen that triggers the majority of asthma exacerbations. The objectives of this study were 1) to evaluate an in vitro air liquid interface cultured human airway epithelial cell model for HRV infection, and 2) to identify gene expression patterns associated with asthma intrinsically and/or after HRV infection using this model. METHODS: Air-liquid interface (ALI) human airway epithelial cell cultures were prepared from 6 asthmatic and 6 non-asthmatic donors...
2015: PloS One
Zheng-Guang Chen, Hui Luo, Shou-Chuan Wang, Jian-Ya Xu, Jia-Xi Li
ETHNOPHARMACOLOGICAL RELEVANCE: Jinxin oral liquid (JOL) is used in traditional Chinese medicine (TCM) to treat influenza, cough, asthma, and viral pneumonia, on the basis of Ma Xing Shi Gan Tang (MXSGT) and the clinical experience of Professor Wang Shouchuan, one of the most prestigious pediatricians in China. AIM OF STUDY: To investigate the anti-inflammatory and antiviral activities of JOL in mice infected with respiratory syncytial virus (RSV). MATERIALS AND METHODS: Mice were orally administered JOL at doses of 27...
March 13, 2015: Journal of Ethnopharmacology
Yung-Chang Su, Dijana Townsend, Lara J Herrero, Ali Zaid, Michael S Rolph, Michelle E Gahan, Michelle A Nelson, Penny A Rudd, Klaus I Matthaei, Paul S Foster, Lindsay Dent, Ralph A Tripp, James Lee, Ljubov Simson, Suresh Mahalingam
UNLABELLED: Human respiratory syncytial virus (RSV) is a major cause of morbidity and severe lower respiratory tract disease in the elderly and very young, with some infants developing bronchiolitis, recurrent wheezing, and asthma following infection. Previous studies in humans and animal models have shown that vaccination with formalin-inactivated RSV (FI-RSV) leads to prominent airway eosinophilic inflammation following RSV challenge; however, the roles of pulmonary eosinophilia in the antiviral response and in disease pathogenesis are inadequately understood...
February 2015: Journal of Virology
Magnus Starkhammar, Olivia Larsson, Susanna Kumlien Georén, Marina Leino, Sven-Erik Dahlén, Mikael Adner, Lars-Olaf Cardell
It is well-established that bacterial and viral infections have an exacerbating effect on allergic asthma, particularly aggravating respiratory symptoms, such as airway hyperresponsiveness (AHR). The mechanism by which these infections alter AHR is unclear, but some studies suggest that Toll-like receptors (TLRs) play a role. In this study, we investigated the impact of TLR3 and TLR4 ligands on AHR and airway inflammation in a model of pre-established allergic inflammation. Female BALB/c mice were sensitised and challenged intranasally (i...
2014: PloS One
J M Birmingham, V L Gillespie, K Srivastava, X-M Li, P J Busse
BACKGROUND: Although morbidity and mortality rates from asthma are highest in patients > 65 years of age, the effect of older age on airway inflammation in asthma is not well established. OBJECTIVE: To investigate age-related differences in the promotion of allergic inflammation after influenza A viral respiratory infection on antigen-specific IgE production, antigen-induced airway inflammation and airway hyperresponsiveness in mice. METHODS: To accomplish this objective, the following model system was used...
September 2014: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
Yutein Chung, Jun Young Hong, Jing Lei, Qiang Chen, J Kelley Bentley, Marc B Hershenson
Rhinovirus (RV) causes asthma exacerbations. Previously, we showed that adherent bronchoalveolar cells from allergen-treated mice produce IL-13 when stimulated with RV ex vivo, implicating cells of the monocyte/macrophage lineage in viral-induced airway inflammation. In this study, we hypothesized that RV infection of allergen-treated mice results in IL-13 production by CD11b+ exudative macrophages in vivo. We sensitized and challenged BALB/c mice with ovalbumin (OVA), after which mice were inoculated with RV or sham HeLa cell lysate...
February 2015: American Journal of Respiratory Cell and Molecular Biology
Yoichi Furuya, Sean Roberts, Gregory J Hurteau, Alan M Sanfilippo, Rachael Racine, Dennis W Metzger
UNLABELLED: Asthma was the most common comorbidity observed among patients hospitalized with influenza A virus during the 2009 pandemic. However, little remains known about how the asthmatic phenotype influences protective immune responses against respiratory viral pathogens. Using the ovalbumin-induced allergic lung inflammation model, we found that asthmatic mice, unlike nonasthmatic mice, were highly susceptible to secondary heterologous virus challenge. While primary virus infection generated protective memory immune responses against homologous secondary virus challenge in both asthmatic and nonasthmatic mice, full protection against heterologous A/California/04/2009 (CA04) viral infection was observed only in nonasthmatic mice...
August 2014: Journal of Virology
C Hawkshaw, J A Scott, C-W Chow, E N Fish
BACKGROUND: The inflammatory immune response associated with allergic airway inflammation in asthma involves T helper type 2 (Th2) immunity. Given the data that a newly described late activator antigen-presenting cell (LAPC) population promotes Th2 immunity in viral infections, we undertook studies to investigate whether LAPCs have a pathogenic role in allergic airway inflammation. METHODS: We employed acute ovalbumin (OVA) and house dust mite (HDM) sensitization and challenge models to establish allergic airway inflammation in mice, followed by the analysis of lungs and draining lymph node (DLN) cell infiltrates, immunoglobulin E (IgE) production, and airway hyper-responsiveness (AHR)...
July 2014: Allergy
Jia Wang, Jinfeng Wu, Lingwen Kong, Muhammat Nurahmat, Meixia Chen, Qingli Luo, Bei Li, Xiao Wu, Jingcheng Dong
ETHNOPHARMACOLOGICAL RELEVANCE: The prevalence of allergic asthma has been increased rapidly in recent years. About 20% of all these sufferers have experienced asthma exacerbation. Although corticosteroids and β-agonists therapy improves serious asthma symptoms, they can׳t completely cure these allergic diseases. BuShenYiQi Formula (BSYQF) has been widely used to treat bronchial asthma and its exacerbation for decades in Huashan Hospital of Fudan University, China. Nevertheless, the mechanisms of BSYQF' anti-asthmatic effects haven׳t been fully elucidated...
May 28, 2014: Journal of Ethnopharmacology
Musa R Khaitov, Igor P Shilovskiy, Aleksandra A Nikonova, Nadezda N Shershakova, Oleg Y Kamyshnikov, Alexander A Babakhin, Vitaly V Zverev, Sebastian L Johnston, Rakhim M Khaitov
Asthma exacerbations are caused primarily by viral infections. Antisense and small interfering RNA (siRNA) technologies have gained attention as potential antiasthma and antiviral approaches. In this study we analyzed whether gene silencing of interleukin (IL)-4 expression and respiratory syncytial virus (RSV) replication by RNA interference is able to suppress allergen- and virus-induced responses in a mouse model of virus-induced asthma exacerbation. Knockdown efficacy of IL-4 siRNA molecules was analyzed in the human HEK293T cell line by cotransfection of six different siRNAs with a plasmid carrying mouse IL-4...
July 2014: Human Gene Therapy
Jennifer A Phan, Anthony Kicic, Luke J Berry, Lynette B Fernandes, Graeme R Zosky, Peter D Sly, Alexander N Larcombe
Human rhinovirus is a key viral trigger for asthma exacerbations. To date, murine studies investigating rhinovirus-induced exacerbation of allergic airways disease have employed systemic sensitisation/intranasal challenge with ovalbumin. In this study, we combined human-rhinovirus infection with a clinically relevant mouse model of aero-allergen exposure using house-dust-mite in an attempt to more accurately understand the links between human-rhinovirus infection and exacerbations of asthma. Adult BALB/c mice were intranasally exposed to low-dose house-dust-mite (or vehicle) daily for 10 days...
2014: PloS One
Jean F Regal, B Paige Lawrence, Alex C Johnson, Sarah J Lojovich, Michael A O'Reilly
BACKGROUND: Infants born prematurely are often treated with supplemental oxygen, which can increase their risk for airway hyper-responsiveness (AHR), asthma, reduced lung function, and altered responses to respiratory viral infections later in childhood. Likewise, exposure of newborn mice to hyperoxia alters baseline pulmonary mechanics and the host response to influenza A virus infection in adult mice. Here, we use this mouse model to test the hypothesis that neonatal hyperoxia also promotes AHR and exacerbated allergen-induced symptoms in adult mice...
March 2014: Pediatric Allergy and Immunology
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