Surface availability of beta-glucans is critical determinant of host immune response toCladosporium cladosporioides

Background It is well accepted that mold exposure is a major contributor to the development of asthma, and beta-glucans are often used as a surrogate for mold exposure in the environment. Beta-glucans are an important component of mold spores and are recognized by the immune system by their receptor, Dectin-1.Cladosporium cladosporioidesspores have a high beta-glucan content, but the beta-glucans are not available on the surface of live spores. Objective We sought to determine whether altering the exposure of beta-glucans inC cladosporioidesthrough heat killing could alter the immune response through binding to Dectin-1. Methods In a murine model of mold-induced asthma, mice were repeatedly exposed to either live or heat-killedC cladosporioidesand the phenotype was determined by the measurement of airway hyperresponsiveness, airway inflammation, and cytokine production. Pro-inflammatory cytokines from dendritic cells were measured by using quantitative PCR and ELISA. Results LiveC cladosporioidesinduced robust airway hyperresponsiveness, eosinophilia, and a predominately TH2 response, while heat-killedC cladosporioidesinduced a strong TH17 response and neutrophilic inflammation, but very mild airway hyperresponsiveness. Heat killing ofC cladosporioidesspores effectively exposed beta-glucans on the surface of the spores and increased binding to Dectin-1. In the absence of Dectin-1, heat-killed spores induced a predominantly TH2 response analogous to live spores. Furthermore, the production of TH17-skewing IL-6, IL-23, and TNF- by dendritic cells in response to heat-killedC cladosporioideswas dependent on Dectin-1. Conclusions The host immune response toC cladosporioidesis dependent on the surface availability of beta-glucans rather than the total beta-glucan content.