HOUSE DUST MITES, BACTERIA AND ASTHMA: THE POTENTIAL MODULATORY ROLE OF GRAM-POSITIVE BACTERIAL PAMPS
Funder
National Health and Medical Research Council
Funding Amount
$518,210.00
Summary
Asthma continues to be a socio-economically important disease with an increasing prevalence. In this regard, allergy to the house dust mite appears to predispose children to the development of the disease although the reasons are unclear. Recently, we discovered and characterised a bacteriolytic enzyme which had previously only been described in pathogenic bacteria, particularly Mycobacteria. In an attempt to determine the origin of the lytic enzyme, we demonstrated that mites also contained a d ....Asthma continues to be a socio-economically important disease with an increasing prevalence. In this regard, allergy to the house dust mite appears to predispose children to the development of the disease although the reasons are unclear. Recently, we discovered and characterised a bacteriolytic enzyme which had previously only been described in pathogenic bacteria, particularly Mycobacteria. In an attempt to determine the origin of the lytic enzyme, we demonstrated that mites also contained a diverse array of Gram-positive bacteria in contrast to Gram-negative bacteria within their guts. Interestingly, the same spectrum of bacterial species were found in carpet and mattress dust from children with asthma. A variety of data suggest exposure to products from Gram-positive organisms may enhance allergic diseases including asthma. In contrast, exposure to products from Gram-negative bacteria is thought to be protective for asthma development. The reasons for the association between Gram-positive bacteria and asthma have not been explored in detail but one potential mechanism that will be explored in this application is the the role of the cell wall constituents which demarcate Gram-positive organisms from Gram-negative organisms as well as sectreted products. The underlying mechanisms involved are likely to reflect a differential ability of the two types of organisms to stimulate the release of divergent immunomodulatory cytokines from cells known to play a role in asthma such as epithelial cells, fibroblasts, T cells and dendritic cells. Data from such studies are likely to greatly increase our understanding of the development of asthma and, therefore, contibute to the development of new treatment modalities with consequent benefit to the community.Read moreRead less
House Dust Mites, Endosymbiotic Bacteria And Asthma
Funder
National Health and Medical Research Council
Funding Amount
$208,372.00
Summary
Asthma is a very common, chronic disease in both children and adults, with a prevalence of at least 5% worldwide. It continues to have a highly significant clinical and socio-economic impact on Western communities, despite the introduction of a variety of pharmacological treatments and there is evidence to indicate that the mortality rate from the disease is increasing. Several sources are known to be associated with asthma but the most frequently associated allergen is the house dust mite (HDM) ....Asthma is a very common, chronic disease in both children and adults, with a prevalence of at least 5% worldwide. It continues to have a highly significant clinical and socio-economic impact on Western communities, despite the introduction of a variety of pharmacological treatments and there is evidence to indicate that the mortality rate from the disease is increasing. Several sources are known to be associated with asthma but the most frequently associated allergen is the house dust mite (HDM) and allergy to it has been shown to be an independent risk factor. Our laboratory has been involved in these studies and have isolated several enzymes associated with digestion. We have also shown that the mite proteases are potent inducers of cytokines from respiratory epithelium, indicating that the biochemistry of allergens may be important in the sensitisation. During these studies, we have shown that mites produce enzymes which lysed Gram-positive bacteria. Analysis of one of these enzymes has revealed that mites are colonised by bacteria in their gut. These bacteria may well be a source of some of the allergens which provoke symptoms in asthmatic patients. In this grant proposal, experiments will be performed to assess this possibility. Such findings may have significant impact on our understanding of mite allergy as well as highlighting potentially new insights into mite control.Read moreRead less