epiglucan and Bronchial-Hyperreactivity

House dust mites (HDM; Dermatophagoides sp.) are one of the commonest aeroallergens worldwide and up to 85% of asthmatics are typically HDM allergic. Allergenicity is associated both with the mites themselves and with ligands derived from mite-associated bacterial and fungal products. Murine models of allergic airways disease for asthma research have recently switched from the use of surrogate allergen ovalbumin together with adjuvant to use of the HDM extract. This has accelerated understanding of how adaptive and innate immunity generate downstream pathology. We review the myriad ways in which HDM allergic responses are orchestrated. Understanding the molecular pathways that elicit HDM-associated pathology is likely to reveal novel targets for therapeutic intervention.

Topics: Adrenal Cortex Hormones; Allergens; Animals; Antigens, Dermatophagoides; Asthma; beta-Glucans; Bronchi; Bronchial Hyperreactivity; Chitin; Cytokines; Dendritic Cells; Disease Models, Animal; Epithelial Cells; Humans; Immunotherapy; Mice; Pyroglyphidae; Respiratory Mucosa; Spores, Fungal; Toll-Like Receptors

Mould exposure has been linked to childhood asthma and bronchial hyper-responsiveness. Few studies have assessed beta-(1,3)-d-glucan (beta-glucan), a significant fungal cell wall constituent, in relation to asthma in adolescence.. To determine whether house dust-derived beta-glucan exposure at age 7-10 is associated with the development and persistence of atopic and non-atopic asthma, and bronchial hyper-responsiveness (BHR) by age 11-14.. Dust samples were collected from the 1995 Study of Asthma, Genes, and Environment (SAGE) birth cohort. This cohort was derived from Manitoba provincial healthcare administrative records of children high and low risk for asthma. Samples were collected from the homes of 422 children at age 7-10 and analyzed using beta-glucan and endotoxin-specific Limulus Amoebocyte Lysate assays. Asthma, atopy, and BHR status of each child were also assessed at ages 7-10 and 11-14.. At age 7-10, beta-glucan dust levels in the home were associated with persistent atopic asthma at age 11-14 (OR 1.79 for each unit increase in levels, 95% CI 1.14-2.81), independent of endotoxin exposure, and Alternaria or Cladosporium sensitization. The likelihood of BHR almost doubled with unit increases in dust beta-glucan in asthmatic children. In children without asthma, exposure to high beta-glucan levels at age 7-10 also elevated risk for BHR in adolescence (OR 1.74, 95% CI 1.05-2.89). New-onset atopic asthma was twice more likely following high beta-glucan exposure in children without asthma but the association did not reach statistical significance. No associations were evident with concurrent asthma phenotype at age 7-10 or non-atopic asthma at age 11-14.. These findings implicate home beta-glucan exposure at school-age as a risk factor for persistent atopic asthma and new-onset BHR. The higher prevalence of BHR in urban adolescents may be propagated by this home exposure.

Topics: Adolescent; Age Factors; Asthma; beta-Glucans; Bronchial Hyperreactivity; Child; Dust; Endotoxins; Environmental Exposure; Female; Humans; Longitudinal Studies; Male; Phenotype; Prevalence; Proteoglycans

There is considerable evidence supporting a role for mold exposure in the pathogenesis and expression of childhood asthma. Aspergillus versicolor and Cladosporium cladosporioides are common molds that have been implicated in asthma. In a model of mold-induced asthma, mice were repeatedly exposed to either A. versicolor or C. cladosporioides spores. The two molds induced distinct phenotypes, and this effect was observed in both BALB/c and C57BL/6 strains. C. cladosporioides induced robust airway hyperresponsiveness (AHR), eosinophilia, and a predominately Th2 response, whereas A. versicolor induced a strong Th17 response and neutrophilic inflammation, but very mild AHR. Neutralization of IL-17A resulted in strong AHR and eosinophilic inflammation following A. versicolor exposure. In Dectin-1-deficient mice, A. versicolor exposure resulted in markedly attenuated IL-17A and robust AHR compared with wild-type mice. In contrast, C. cladosporioides induced AHR and eosinophilic inflammation independent of IL-17A and Dectin-1. A. versicolor, but not C. cladosporioides, spores had increased exposure of β-glucans on their surface and were able to bind Dectin-1. Thus, the host response to C. cladosporioides was IL-17A- and Dectin-1-independent, whereas Dectin-1- and IL-17A-dependent pathways were protective against the development of asthma after exposure to A. versicolor.

Topics: Animals; Anti-Asthmatic Agents; Aspergillus; Asthma; beta-Glucans; Bronchial Hyperreactivity; Cladosporium; Eosinophils; Immunophenotyping; Inflammation Mediators; Interleukin-17; Lectins, C-Type; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Neutrophils; Spores, Fungal; Surface Properties

A number of studies have suggested a correlation between a decreased incidence in infectious diseases and an increased incidence of allergic diseases, including asthma. Although several pathogen-derived products have been shown to possess therapeutic potential for allergic diseases, it remains largely unknown whether β-glucan, a cell wall component of a variety of fungi, yeasts, and bacteria, has a regulatory potential for allergic diseases. In this study, we examined the effect of curdlan, a linear β-(1-3)-glucan, on the development of allergic airway inflammation. We found that i.p. injection of curdlan significantly inhibited Ag-induced eosinophil recruitment and Th2 cytokine production in the airways. The activation of CD4(+) T cells in the presence of curdlan induced IL-10-producing CD4(+) T cells with high levels of c-Maf expression. Curdlan-induced development of IL-10-producing CD4(+) T cells required the presence of APCs and ICOS/ICOS ligand interaction. Curdlan-induced development of IL-10-producing CD4(+) T cells also required intrinsic expression of STAT6. Furthermore, the transfer of Ag-specific CD4(+) T cells that were stimulated in the presence of curdlan inhibited Ag-induced eosinophil recruitment into the airways. Taken together, these results suggest that curdlan is capable of inducing IL-10-producing CD4(+) T cells and inhibiting the development of eosinohilic airway inflammation, underscoring the therapeutic potential of curdlan for allergic diseases.

Topics: Animals; beta-Glucans; Bronchial Hyperreactivity; CD4-Positive T-Lymphocytes; Cells, Cultured; Eosinophilia; Inflammation Mediators; Injections, Intraperitoneal; Interleukin-10; Mice; Mice, Inbred BALB C; Mice, Transgenic; Respiratory Hypersensitivity

Divergent results have been reported regarding early life exposure to indoor environmental agents and the risk of asthma and allergic sensitization later in life.. To assess whether early exposure to indoor allergens, beta(1,3)-glucans and endotoxin modifies the risk of allergic diseases at 10 years of age.. The concentrations of mite, cat and dog allergens, endotoxin and beta(1,3)-glucans were determined in dust from the homes of 260 two-year-old children with lung function measured at birth (tidal flow volume loops) in the Environment and Childhood Asthma study in Oslo. At 10 years, the health status was assessed in a follow-up study including a structured interview of the parents and an extended clinical examination.. Cat and dog keeping at 2 years of age was reported in 6.5% and 5.5% of the families, respectively. Mite allergens were detected in only 4/260 dust samples. The adjusted odds ratio for asthma at age 10 was 1.20 (95% confidence interval: 1.01-1.43) and 1.22 (1.02-1.46) for bronchial hyperresponsiveness (BHR) per 10 microg/g dust increase in cat allergen exposure at 2 years of age. No association was seen with allergic sensitization. Moreover, endotoxin and beta(1,3)-glucan exposure did not modify the risk of asthma or allergic sensitization. None of the measured environmental factors were associated with lung function at 10 years of age or a relative change in lung function from birth.. In a community with a low prevalence of pet keeping and low mite allergen levels, exposure to cat allergens early in life increased the risk of late childhood asthma and BHR, but not the risk of allergic sensitization. No risk modification was seen for dog allergens, endotoxin and beta(1,3)-glucans.

Topics: Allergens; Animals; Animals, Domestic; Asthma; beta-Glucans; Bronchial Hyperreactivity; Cats; Child; Child, Preschool; Dogs; Endotoxins; Environmental Exposure; Female; Follow-Up Studies; Humans; Male; Proteoglycans; Pyroglyphidae; Risk Factors