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Rhinovirus challenge model

S J Rachman
The construct of the psychological immune system is described and analysed. The direct and indirect cognitive influences on the system are discussed, and the implications of adding a cognitive construal to the influential model of a behavioural immune system are considered. The psychological immune system has two main properties: defensive and healing. It encompasses a good amount of health-related phenomena that is outside the scope of the behavioural model or the biological immune system. Evidence pertaining to the psychological immune system includes meta-analyses of the associations between psychological variables such as positive affect/wellbeing and diseases and mortality, and associations between wellbeing and positive health...
December 2016: Journal of Behavior Therapy and Experimental Psychiatry
Alison R Hill, Jessica E Donaldson, Cornelia Blume, Natalie Smithers, Liku Tezera, Kamran Tariq, Patrick Dennison, Hitasha Rupani, Matthew J Edwards, Peter H Howarth, Christopher Grainge, Donna E Davies, Emily J Swindle
The bronchial epithelium and underlying fibroblasts form an epithelial mesenchymal trophic unit (EMTU) which controls the airway microenvironment. We hypothesized that cell-cell communication within the EMTU propagates and amplifies the innate immune response to respiratory viral infections. EMTU co-culture models incorporating polarized (16HBE14o-) or differentiated primary human bronchial epithelial cells (HBECs) and fibroblasts were challenged with double-stranded RNA (dsRNA) or rhinovirus. In the polarized EMTU model, dsRNA affected ionic but not macromolecular permeability or cell viability...
July 2016: Tissue Barriers
Sung Bu Lee, Jeong-Ah Song, Go-Eun Choi, Hun Sik Kim, Yong Ju Jang
BACKGROUND: Patients with chronic rhinosinusitis (CRS) commonly experience aggravation of their symptoms after viral upper respiratory infection (URI). Rhinovirus (RV) is the most common URI-causing virus. However, there is a lack of a mouse model of RV infection and in vivo studies investigating the effect of RV infection on CRS. METHODS: A mouse model of chronic allergic rhinosinusitis (CARS) was established by sensitizing to ovalbumin (OVA) through intraperitoneal injection followed by nasal challenges with OVA for 5 weeks...
June 27, 2016: International Forum of Allergy & Rhinology
Klaus Bønnelykke, Carole Ober
Asthma is a heterogeneous clinical syndrome that includes subtypes of disease with different underlying causes and disease mechanisms. Asthma is caused by a complex interaction between genes and environmental exposures; early-life exposures in particular play an important role. Asthma is also heritable, and a number of susceptibility variants have been discovered in genome-wide association studies, although the known risk alleles explain only a small proportion of the heritability. In this review, we present evidence supporting the hypothesis that focusing on more specific asthma phenotypes, such as childhood asthma with severe exacerbations, and on relevant exposures that are involved in gene-environment interactions (GEIs), such as rhinovirus infections, will improve detection of asthma genes and our understanding of the underlying mechanisms...
March 2016: Journal of Allergy and Clinical Immunology
M Kumpu, R A Kekkonen, R Korpela, S Tynkkynen, S Järvenpää, H Kautiainen, E K Allen, J O Hendley, A Pitkäranta, B Winther
The aim of this work was to investigate the usability of an experimental rhinovirus model in probiotic trials aiming to assess effectiveness in viral infections, and to provide preliminary data of live and inactivated probiotic Lactobacillus rhamnosus GG for larger-scale trials utilising the model. 59 subjects were randomised to receive 100 ml of fruit juice supplemented with 10(9) cfu of live or heat-inactivated (by spray-drying) L. rhamnosus GG or control juice daily for six weeks. After three weeks subjects were intranasally inoculated with experimental rhinovirus...
2015: Beneficial Microbes
Luke Hatchwell, Adam Collison, Jason Girkin, Kristy Parsons, Junyao Li, Jie Zhang, Simon Phipps, Darryl Knight, Nathan W Bartlett, Sebastian L Johnston, Paul S Foster, Peter A B Wark, Joerg Mattes
BACKGROUND: Asthma exacerbations represent a significant disease burden and are commonly caused by rhinovirus (RV), which is sensed by Toll-like receptors (TLR) such as TLR7. Some asthmatics have impaired interferon (IFN) responses to RV, but the underlying mechanisms of this clinically relevant observation are poorly understood. OBJECTIVES: To investigate the importance of intact TLR7 signalling in vivo during RV exacerbation using mouse models of house dust mite (HDM)-induced allergic airways disease exacerbated by a superimposed RV infection...
September 2015: Thorax
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
Jorge C G Blanco, Susan Core, Lioubov M Pletneva, Thomas H March, Marina S Boukhvalova, Adriana E Kajon
Human rhinoviruses (HRV) represent the single most important etiological agents of the common cold and are the most frequent cause of acute respiratory infections in humans. Currently the performance of available animal models for immunization studies using HRV challenge is very limited. The cotton rat (Sigmodon hispidus) is a well-recognized model for the study of human respiratory viral infections. In this work we show that, without requiring any genetic modification of either the host or the virus, intranasal infection of cotton rats with HRV16 resulted in measurable lower respiratory tract pathology, mucus production, and expression of interferon-activated genes...
2014: Trials in Vaccinology
Jun Young Hong, Yutein Chung, Jessica Steenrod, Qiang Chen, Jing Lei, Adam T Comstock, Adam M Goldsmith, J Kelley Bentley, Uma S Sajjan, Marc B Hershenson
BACKGROUND: The mechanisms by which viruses cause asthma exacerbations are not precisely known. Previously, we showed that, in ovalbumin (OVA)-sensitized and -challenged mice with allergic airway inflammation, rhinovirus (RV) infection increases type 2 cytokine production from alternatively-activated (M2) airway macrophages, enhancing eosinophilic inflammation and airways hyperresponsiveness. In this paper, we tested the hypothesis that IL-4 signaling determines the state of macrophage activation and pattern of RV-induced exacerbation in mice with allergic airways disease...
2014: Respiratory Research
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
Joshua L Kennedy, Marcus Shaker, Victoria McMeen, James Gern, Holliday Carper, Deborah Murphy, Wai-Ming Lee, Yury A Bochkov, Rose F Vrtis, Thomas Platts-Mills, James Patrie, Larry Borish, John W Steinke, William A Woods, Peter W Heymann
RATIONALE: Most virus-induced attacks of asthma are caused by rhinoviruses (RVs). OBJECTIVES: To determine whether people with asthma are susceptible to an increased viral load during RV infection. METHODS: Seventy-four children (4-18 yr old) were enrolled; 28 with wheezing, 32 with acute rhinitis, and 14 without respiratory tract symptoms. Nasal washes were evaluated using quantitative polymerase chain reaction for RV to judge viral load along with gene sequencing to identify strains of RV...
March 1, 2014: American Journal of Respiratory and Critical Care Medicine
Luke Hatchwell, Jason Girkin, Matthew D Dun, Matthew Morten, Nicole Verrills, Hamish D Toop, Jonathan C Morris, Sebastian L Johnston, Paul S Foster, Adam Collison, Joerg Mattes
BACKGROUND: β-Agonists are used for relief and control of asthma symptoms by reversing bronchoconstriction. They might also have anti-inflammatory properties, but the underpinning mechanisms remain poorly understood. Recently, a direct interaction between formoterol and protein phosphatase 2A (PP2A) has been described in vitro. OBJECTIVE: We sought to elucidate the molecular mechanisms by which β-agonists exert anti-inflammatory effects in allergen-driven and rhinovirus 1B-exacerbated allergic airways disease (AAD)...
June 2014: Journal of Allergy and Clinical Immunology
Eugene Kim, Huisu Lee, Hyun Sook Kim, Sulmui Won, Eu Kyoung Lee, Hwan Soo Kim, Kyongwon Bang, Yoon Hong Chun, Jong-Seo Yoon, Hyun Hee Kim, Jin Tack Kim, Joon Sung Lee
PURPOSE: The aim of the present study was to investigate the differences in lower airway inflammatory immune responses, including cellular responses and responses in terms of inflammatory mediators in bronchoalveolar lavage fluid (BALF) and the airway, to rhinovirus (RV) infection on asthma exacerbation by comparing a control and a murine asthma model, with or without RV infection. METHODS: BALB/c mice were intraperitoneally injected with a crude extract of Dermatophagoides farinae (Df) or phosphate buffered saline (PBS) and were subsequently intranasally treated with a crude extract of Df or PBS...
November 2013: Korean Journal of Pediatrics
I Mahmutovic-Persson, H Akbarshahi, N W Bartlett, N Glanville, S L Johnston, A Brandelius, L Uller
BACKGROUND: Rhinovirus infection or dsRNA stimulation increased thymic stromal lymphopoietin (TSLP), an upstream pro-allergic cytokine, in asthmatic bronchial epithelial cells. We hypothesized that dsRNA challenges superimposed on established experimental allergic asthma constitute a useful exacerbation model. We further hypothesized that TSLP is induced at dsRNA- and rhinoviral infection-induced exacerbations. METHODS: Allergic mice were challenged with OVA followed by three daily intranasal challenges with dsRNA or saline...
March 2014: Allergy
Deborah L Clarke, Nicola H E Davis, Jayesh B Majithiya, Sian C Piper, Arthur Lewis, Matthew A Sleeman, Dominic J Corkill, Richard D May
Viral respiratory tract infections are known triggers of asthma exacerbations in both adults and children. The current standard of care, inhaled CS (corticosteroids) and LABAs (long-acting β2-adrenoceptor agonists), fails to prevent the loss of control that manifests as an exacerbation. In order to better understand the mechanisms underlying viral asthma exacerbations we established an in vivo model using the clinically relevant aeroallergen HDM (house dust mite) and the viral mimetic/TLR3 (Toll-like receptor 3) agonist poly(I:C)...
April 2014: Clinical Science (1979-)
Dina Schneider, Jun Young Hong, Emily R Bowman, Yutein Chung, Deepti R Nagarkar, Christina L McHenry, Adam M Goldsmith, J Kelley Bentley, Toby C Lewis, Marc B Hershenson
Human rhinovirus (HRV) infections lead to exacerbations of lower airways disease in asthmatic patients but not in healthy individuals. However, underlying mechanisms remain to be completely elucidated. We hypothesized that the Th2-driven allergic environment enhances HRV-induced CC chemokine production, leading to asthma exacerbations. Ovalbumin (OVA)-sensitized and -challenged mice inoculated with HRV showed significant increases in the expression of lung CC chemokine ligand (CCL)-2/monocyte chemotactic protein (MCP)-1, CCL4/macrophage inflammatory protein (MIP)-1β, CCL7/MCP-3, CCL19/MIP-3β, and CCL20/MIP3α compared with mice treated with OVA alone...
February 1, 2013: American Journal of Physiology. Lung Cellular and Molecular Physiology
Benjamin L Unger, Andrea N Faris, Shyamala Ganesan, Adam T Comstock, Marc B Hershenson, Umadevi S Sajjan
Bacterial infections following rhinovirus (RV), a common cold virus, are well documented, but pathogenic mechanisms are poorly understood. We developed animal and cell culture models to examine the effects of RV on subsequent infection with non-typeable Hemophilus influenzae (NTHi). We focused on NTHI-induced neutrophil chemoattractants expression that is essential for bacterial clearance. Mice infected with RV1B were superinfected with NTHi and lung bacterial density, chemokines and neutrophil counts determined...
2012: PLoS Pathogens
René van der Merwe, Nestor A Molfino
Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Current therapies confer partial benefits either by incompletely improving airflow limitation or by reducing acute exacerbations, hence new therapies are desirable. In the absence of robust early predictors of clinical efficacy, the potential success of novel therapeutic agents in COPD will not entirely be known until the drugs enter relatively large and costly clinical trials. New predictive models in humans, and new study designs are being sought to allow for confirmation of pharmacodynamic and potentially clinically meaningful effects in early development...
2012: International Journal of Chronic Obstructive Pulmonary Disease
Rodlescia S Sneed, Sheldon Cohen, Ronald B Turner, William J Doyle
OBJECTIVE: To determine whether parenthood predicts host resistance to the common cold among healthy volunteers experimentally exposed to a common cold virus. METHODS: Participants were 795 healthy volunteers (age range = 18-55 years) enrolled in one of three viral-challenge studies conducted from 1993 to 2004. After reporting parenthood status, participants were quarantined, administered nasal drops containing one of four common cold viruses, and monitored for the development of a clinical cold (infection in the presence of objective signs of illness) on the day before and for 5 to 6 days after exposure...
July 2012: Psychosomatic Medicine
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