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Viral asthma challenge model

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https://www.readbyqxmd.com/read/28947081/chronic-il-33-expression-predisposes-to-viral-induced-exacerbations-of-asthma-by-increasing-type-2-inflammation-and-dampening-antiviral-immunity
#1
Rhiannon B Werder, B Biomed Sci, Vivian Zhang, Jason P Lynch, Natale Snape, John W Upham, Kirsten Spann, Simon Phipps
BACKGROUND: Rhinovirus infection triggers acute exacerbations of asthma. IL-33 is an instructive cytokine of type-2 inflammation whose expression is associated with viral load during experimental rhinovirus infection of asthmatic subjects. OBJECTIVE: To determine whether anti-IL-33 therapy is effective during disease progression, established disease, or viral exacerbation using a preclinical model of chronic asthma and in vivo human primary airway epithelial cells (AECs)...
September 22, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28742120/virus-induced-asthma-attack-the-importance-of-allergic-inflammation-in-response-to-viral-antigen-in-an-animal-model-of-asthma
#2
Christopher Skappak, Ramses Ilarraza, Ying-Qi Wu, Matthew G Drake, Darryl J Adamko
Asthma exacerbation can be a life-threatening condition, and is most often triggered by common respiratory viruses. Poor asthma control and worsening of respiratory function is associated with increased airway inflammation, including eosinophilia. Prevention of asthma exacerbation relies on treatment with corticosteroids, which preferentially inhibit allergic inflammation like eosinophils. Human studies demonstrate that inactivated virus can trigger eosinophil activation in vitro through antigen presentation and memory CD4+ lymphocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28647381/leukotriene-receptor-antagonist-attenuated-airway-inflammation-and-hyperresponsiveness-in-a-double-stranded-rna-induced-asthma-exacerbation-model
#3
Mariko Ujino, Naoya Sugimoto, Yuta Koizumi, Shoki Ro, Yasuhiro Kojima, Kamiyama-Hara Asae, Naomi Yamashita, Ken Ohta, Hiroyuki Nagase
BACKGROUND: Viral infections are the most common triggers of asthma exacerbation, but the key molecules involved in this process have not been fully identified. Although cysteinyl leukotrienes (cysLTs) have been postulated as the key mediators, their precise roles remain largely unclear. To investigate the roles of cysLTs in virus-induced asthma exacerbation, we developed a murine model using a viral double-stranded RNA analog, polyinosinic-polycytidylic acid (poly I:C), and analyzed the effect of leukotriene receptor antagonist (LTRA) administration...
June 21, 2017: Allergology International: Official Journal of the Japanese Society of Allergology
https://www.readbyqxmd.com/read/28474108/the-immunotherapeutic-role-of-bacterial-lysates-in-a-mouse-model-of-asthma
#4
Chentao Liu, Rong Huang, Rujie Yao, Aimei Yang
INTRODUCTION: Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Recurrent respiratory tract infections in young children, especially viral infections, are the major cause of acute asthmatic exacerbations and contribute to development of asthma. Bacterial extracts have been used to improve the immune defenses of the respiratory tract. However, seldom studies have examined the effect of bacterial lysates on childhood asthma. In this study, we examined whether bacterial lysates (OM-85) will improve symptoms of asthmatic mice via modulation of the immune response...
May 4, 2017: Lung
https://www.readbyqxmd.com/read/28397284/altered-fatty-acid-metabolism-and-reduced-stearoyl-coenzyme-a-desaturase-activity-in-asthma
#5
N Rodriguez-Perez, E Schiavi, R Frei, R Ferstl, P Wawrzyniak, S Smolinska, M Sokolowska, N A Sievi, M Kohler, P Schmid-Grendelmeier, D Michalovich, K D Simpson, E M Hessel, M Jutel, M Martin-Fontecha, O Palomares, C A Akdis, L O'Mahony
BACKGROUND: Fatty acids and lipid mediator signaling play an important role in the pathogenesis of asthma, yet this area remains largely underexplored. The aims of this study were (i) to examine fatty acid levels and their metabolism in obese and nonobese asthma patients and (ii) to determine the functional effects of altered fatty acid metabolism in experimental models. METHODS: Medium- and long-chain fatty acid levels were quantified in serum from 161 human volunteers by LC/MS...
April 11, 2017: Allergy
https://www.readbyqxmd.com/read/28283567/eosinophils-promote-antiviral-immunity-in-mice-infected-with-influenza-a-virus
#6
Amali E Samarasinghe, Rossana C N Melo, Susu Duan, Kim S LeMessurier, Swantje Liedmann, Sherri L Surman, James J Lee, Julia L Hurwitz, Paul G Thomas, Jonathan A McCullers
Eosinophils are multifunctional cells of the innate immune system linked to allergic inflammation. Asthmatics were more likely to be hospitalized but less likely to suffer severe morbidity and mortality during the 2009 influenza pandemic. These epidemiologic findings were recapitulated in a mouse model of fungal asthma wherein infection during heightened allergic inflammation was protective against influenza A virus (IAV) infection and disease. Our goal was to delineate a mechanism(s) by which allergic asthma may alleviate influenza disease outcome, focused on the hypothesis that pulmonary eosinophilia linked with allergic respiratory disease is able to promote antiviral host defenses against the influenza virus...
April 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27936016/a-tool-for-investigating-asthma-and-copd-exacerbations-a-newly-manufactured-and-well-characterised-gmp-wild-type-human-rhinovirus-for-use-in-the-human-viral-challenge-model
#7
RANDOMIZED CONTROLLED TRIAL
Daniel J Fullen, Bryan Murray, Julie Mori, Andrew Catchpole, Daryl W Borley, Edward J Murray, Ganesh Balaratnam, Anthony Gilbert, Alex Mann, Fiona Hughes, Rob Lambkin-Williams
BACKGROUND: Human Rhinovirus infection is an important precursor to asthma and chronic obstructive pulmonary disease exacerbations and the Human Viral Challenge model may provide a powerful tool in studying these and other chronic respiratory diseases. In this study we have reported the production and human characterisation of a new Wild-Type HRV-16 challenge virus produced specifically for this purpose. METHODS AND STOCK DEVELOPMENT: A HRV-16 isolate from an 18 year old experimentally infected healthy female volunteer (University of Virginia Children's Hospital, USA) was obtained with appropriate medical history and consent...
2016: PloS One
https://www.readbyqxmd.com/read/27916086/-recombinant-adenovirus-type-5-does-not-aggravate-asthma-symptoms-in-a-mouse-model-of-ovalbumin-induced-asthma
#8
Zhengling Zhang, Yiling Zhang, Jing Han, Ping Lu, Lin Xu
Objective To explore the effect of recombinant adenovirus type 5 (rAd5) on a mouse model of ovalbumin (OVA)-induced asthma. Methods Sixty female C57BL/6 mice (6-8 weeks old and 18-20 g) were randomly divided into 4 groups: healthy control group, rAd5 control group, OVA asthma control group and OVA asthma group with rAd5 immunization. 15 mice in each group. The mice in the OVA asthma control group and the OVA asthma group with rAd5 immunization were sensitized by intraperitoneal injection of 50 μg OVA emulsified in 2 mg of aluminum potassium sulfate on day 0, 7 and 14; subsequently, the mice in the two groups were exposed to OVA aerosol challenge for 3 consecutive days (on day 42, 43 and 44)...
December 2016: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/27128804/smoke-and-viruses-a-hindrance-to-relaxing-the-airways
#9
COMMENT
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-)
https://www.readbyqxmd.com/read/27036916/tnf-%C3%AE-and-macrophages-are-critical-for-respiratory-syncytial-virus-induced-exacerbations-in-a-mouse-model-of-allergic-airways-disease
#10
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
https://www.readbyqxmd.com/read/26879906/increased-expression-of-upstream-th2-cytokines-in-a-mouse-model-of-viral-induced-asthma-exacerbation
#11
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...
February 16, 2016: Journal of Translational Medicine
https://www.readbyqxmd.com/read/26407325/prevention-of-influenza-virus-induced-immunopathology-by-tgf-%C3%AE-produced-during-allergic-asthma
#12
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
https://www.readbyqxmd.com/read/26333698/models-of-respiratory-infections-virus-induced-asthma-exacerbations-and-beyond
#13
REVIEW
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
https://www.readbyqxmd.com/read/26245201/double-stranded-rna-evokes-exacerbation-in-a-mouse-model-of-corticosteroid-refractory-asthma
#14
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-)
https://www.readbyqxmd.com/read/25992862/klf4-expression-in-conventional-dendritic-cells-is-required-for-t-helper-2-cell-responses
#15
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
https://www.readbyqxmd.com/read/25847914/comprehensive-evaluation-of-poly-i-c-induced-inflammatory-response-in-an-airway-epithelial-model
#16
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
https://www.readbyqxmd.com/read/25706956/phenotypic-responses-of-differentiated-asthmatic-human-airway-epithelial-cultures-to-rhinovirus
#17
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
https://www.readbyqxmd.com/read/25593018/antiviral-effects-of-jinxin-oral-liquid-against-respiratory-syncytial-virus-infection-in-the-balb-c-mice-model
#18
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
https://www.readbyqxmd.com/read/25410867/dual-proinflammatory-and-antiviral-properties-of-pulmonary-eosinophils-in-respiratory-syncytial-virus-vaccine-enhanced-disease
#19
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
https://www.readbyqxmd.com/read/25089623/toll-like-receptor-ligands-lps-and-poly-i-c-exacerbate-airway-hyperresponsiveness-in-a-model-of-airway-allergy-in-mice-independently-of-inflammation
#20
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
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