title: Surface availability of beta-glucans is critical determinant of host immune response to Cladosporium cladosporioides.
abstract: 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 cladosporioides spores 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 in C cladosporioides through 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-killed C cladosporioides and 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
  Live C cladosporioides induced robust airway hyperresponsiveness, eosinophilia, and a predominately TH2 response, while heat-killed C cladosporioides induced a strong TH17 response and neutrophilic inflammation, but very mild airway hyperresponsiveness. Heat killing of C cladosporioides spores 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-α by dendritic cells in response to heat-killed C cladosporioides was dependent on Dectin-1.
  
  
  CONCLUSIONS
  The host immune response to C cladosporioides is dependent on the surface availability of beta-glucans rather than the total beta-glucan content.
authors: Division of Asthma Research, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors: Rachael A
authors: RA
authors: Mintz-Cole
authors: Eric B
authors: EB
authors: Brandt
authors: Stacey A
authors: SA
authors: Bass
authors: Aaron M
authors: AM
authors: Gibson
authors: Tiina
authors: T
authors: Reponen
authors: Gurjit K
authors: GK
authors: Khurana Hershey
mesh_terms: D000818:Animals; D001249:Asthma / Q000517:prevention & control; D002963:Cladosporium / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology; D037181:Lectins, C-Type / Q000502:physiology; D008168:Lung / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000502:physiology; D013172:Spores, Fungal / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D047071:beta-Glucans / Q000378:metabolism*; D000099181:Dectin-1
chemical_list: D016207:Cytokines; D037181:Lectins, C-Type; D047071:beta-Glucans; D000099181:Dectin-1
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