Academic literature on the topic 'House dust mite extracts'

Asthma is a chronic inflammatory disease of the airways and is characterised by airway hyperresponsiveness (AHR), inflammation and remodelling. House dust mite (HDM; Dermatophagoides pteronyssinus) is a complex aeroallergen, commonly associated with development of allergic asthma. Animal models have been utilised extensively to model the traits of asthma and HDM-induced allergic airways disease was established in mice following serial HDM challenge via the respiratory mucosa. Mice exposed to HDM developed pulmonary eosinophilia, characterised by Th2 cytokine production, concomitant with AHR and airway remodelling. Following the establishment and characterisation of this model of allergic airways disease, it was next investigated which features of the HDM allergen were responsible for disease pathogenesis. Using genetically modified mice and pharmacological approaches, it was found that the TLR-TRIF signalling pathway played a crucial role in HDM-induced allergic airways disease. Intrinsic protease activity of the HDM extract was also observed to be vital for disease pathogenesis, whereby mice exposed to boiled HDM developed a less severe asthma phenotype. Utilising a pan neutralising antibody directed towards transforming growth factor-β (TGF-β), TGF-β was shown to play a critical role in regulating HDM-induced airway inflammation in vivo. Following therapeutic blockade of TGF-β, the numbers of CD4+CD25+FoxP3+ regulatory T cells and CD4+IL-10+ cells were decreased resulting in exacerbation of AHR and BAL inflammation compared to HDM-treated isotype control mice. However, HDM-induced airway remodelling progressed independently of TGF-β. In conclusion, it has been determined that HDM-induced Th2-driven inflammation, AHR and airway remodelling in mice is induced by multiple features of the allergen and that TGF-β regulates HDM-driven airway inflammation. Thus these findings provide an insight into the mechanisms by which the aeroallergen HDM promotes allergic disease and will aid in the development of potential new therapeutic strategies for the treatment of asthma.

A disproportionately large number of asthmatics experienced morbidity and mortality during the 2009 H1N1 pandemic. To date, there is little information on the mechanisms behind this epidemiological and clinical observation. Using a murine asthma model, we sought to determine the effects of airway inflammation on host responses to pandemic H1N1 (pH1N1) infection. We hypothesized that mice with an allergic airway phenotype would have a greater viral susceptibility to pH1N1 infection and a dysregulated host response that prevents effective viral clearance and leads to increased burden of pulmonary inflammation, resulting in poor clinical outcomes. We established a murine allergic airway model using house dust mite (HDM) extract. We intranasally instilled male BALB/c mice with HDM or sham PBS daily for two weeks; after which we introduced a single intranasal dose of pH1N1 virus or control vehicle fluid (CAF). HDM or PBS instillation continued daily post-viral infection (pi) forming four groups: 1) sham-sensitized + CAF, 2) HDM-sensitized + CAF, 3) sham-sensitized + pH1N1, and 4) HDM-sensitized + pH1N1. Mice were weighed daily. Virus-infected animals were euthanized at 1-hr pi and on Day 1, 2, 4, 5, 6, and 8 pi and non-infected animals were euthanized on Day 0 and 8 pi. Viral titre, interferon-β (IFN β), and interferon-stimulated gene (ISG) expression patterns were determined by qPCR on RNA extracted from homogenized lung tissue. IFN β protein levels were evaluated by ELISA in bronchoalveolar lavage. Pulmonary inflammation was quantified using H&E stain on formalin-fixed paraffin-embedded lung tissue. HDM-sensitized animals exhibited significantly greater weight loss than sham-sensitized animals following infection. Also, HDM-sensitized mice had significantly higher viral titres on Day 8 pi as compared to sham-sensitized mice. Downstream ISG inductions were dampened in HDM-sensitized, virus-infected animals despite comparable initial IFN β response in HDM- and sham-sensitized mice. We also observed mixed-type pulmonary inflammation in HDM-sensitized mice following pH1N1 infection. Our data suggest dysregulated host ISG responses, combined with the overwhelming burden of pulmonary inflammation, contribute to impaired viral clearance and weight loss indicative of detrimental health outcomes in animals sensitized with HDM following pH1N1 infection.<br>Medicine, Faculty of<br>Experimental Medicine, Division of<br>Medicine, Department of<br>Graduate