Dataset Information

?-Glucan exacerbates allergic asthma independent of fungal sensitization and promotes steroid-resistant TH2/TH17 responses.

ABSTRACT: BACKGROUND:Allergic sensitization to fungi has been associated with asthma severity. As a result, it has been largely assumed that the contribution of fungi to allergic disease is mediated through their potent antigenicity. OBJECTIVE:We sought to determine the mechanism by which fungi affect asthma development and severity. METHODS:We integrated epidemiologic and experimental asthma models to explore the effect of fungal exposure on asthma development and severity. RESULTS:We report that fungal exposure enhances allergen-driven TH2 responses, promoting severe allergic asthma. This effect is independent of fungal sensitization and can be reconstituted with ?-glucan and abrogated by neutralization of IL-17A. Furthermore, this severe asthma is resistant to steroids and characterized by mixed TH2 and TH17 responses, including IL-13+IL-17+CD4+ double-producing effector T cells. Steroid resistance is dependent on fungus-induced TH17 responses because steroid sensitivity was restored in IL-17rc-/- mice. Similarly, in children with asthma, fungal exposure was associated with increased serum IL-17A levels and asthma severity. CONCLUSION:Our data demonstrate that fungi are potent immunomodulators and have powerful effects on asthma independent of their potential to act as antigens. Furthermore, our results provide a strong rationale for combination treatment strategies targeting IL-17A for this subgroup of fungus-exposed patients with difficult-to-treat asthma.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC5073040 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Publications

β-Glucan exacerbates allergic asthma independent of fungal sensitization and promotes steroid-resistant T<sub>H</sub>2/T<sub>H</sub>17 responses.

Zhang Zhonghua Z Biagini Myers Jocelyn M JM Brandt Eric B EB Ryan Patrick H PH Lindsey Mark M Mintz-Cole Rachael A RA Reponen Tiina T Vesper Stephen J SJ Forde Frank F Ruff Brandy B Bass Stacey A SA LeMasters Grace K GK Bernstein David I DI Lockey James J Budelsky Alison L AL Khurana Hershey Gurjit K GK

The Journal of allergy and clinical immunology 20160420 1

<h4>Background</h4>Allergic sensitization to fungi has been associated with asthma severity. As a result, it has been largely assumed that the contribution of fungi to allergic disease is mediated through their potent antigenicity.<h4>Objective</h4>We sought to determine the mechanism by which fungi affect asthma development and severity.<h4>Methods</h4>We integrated epidemiologic and experimental asthma models to explore the effect of fungal exposure on asthma development and severity.<h4>Resul ...[more]

PMID: 27221135

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Project description:BackgroundSpecific patterns of allergic sensitization as well as quantification of the in vitro IgE response in early life may provide relevant clinical insight into future rhinitis and asthma risk.ObjectiveTo define relationships among established sensitization to particular aeroallergens, quantitative analyses of allergen-specific IgE levels, pet exposure and sensitization, and asthma and rhinitis risk.MethodsChildren at high-risk for the development of asthma and allergic diseases were enrolled at birth into the Childhood Origins of ASThma (COAST) study. Allergen-specific IgE was assessed at ages 1, 3, 6, and 9 years by fluoroenzyme immunoassay (Unicap(®) 100; Pharmacia Diagnostics). Current asthma and rhinitis were diagnosed at age 6 and 8 years.ResultsSensitization to dog was strongly associated with increased asthma risk (P < 0.0001). Sensitization to perennial compared with seasonal allergens was more strongly associated with asthma risk, while sensitization to seasonal allergens was more closely associated with rhinitis risk. Increased levels of specific IgE to perennial allergens were associated with an increased asthma risk (P = 0.05), while any detectable level of IgE to seasonal allergens was associated with increased rhinitis risk (P = 0.0009). While dog and cat sensitization were both independently associated with increased asthma and rhinitis risk, dog exposure at birth was associated with a reduced risk of asthma, regardless of dog sensitization status during the first 6 years of life (P = 0.05).Conclusions and clinical relevanceAnalysing specific patterns of an individual's allergic sensitization profile reveals additional relevant associations with asthma and rhinitis risk as opposed to the information gained from characterizing an individual as 'atopic' by the presence of any demonstrable sensitization alone. Furthermore, protective mechanisms of dog exposure with regards to asthma risk appear to be unrelated to the prevention of sensitization.

Dataset Information

?-Glucan exacerbates allergic asthma independent of fungal sensitization and promotes steroid-resistant TH2/TH17 responses.

Publications

β-Glucan exacerbates allergic asthma independent of fungal sensitization and promotes steroid-resistant T<sub>H</sub>2/T<sub>H</sub>17 responses.

Similar Datasets

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