Dectin-1 and IL-17A Suppress Murine Asthma Induced by Aspergillus versicolor but Not Cladosporium cladosporioides Due to Differences in b-Glucan Surface Exposure

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 b-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. A sthma is a major public health problem affecting nearly 23 million people in the United States, including 7 million children (1, 2). It is a complex disease with both genetic and enviromental factors contributing to disease patho-gensis, and mold exposure has been implicated in the development and prevalence of asthma. In 2007, nearly half of the weekly requests received by the National Institute for Occupational Safety and Health concerned work-related asthma and mold exposure (3). In the Cincinnati Childhood Allergy and Air Pollution Study longitudinal birth cohort, mold exposure was associated with increased incidence of wheeze in infants (4), increased risk of developing asthma at age 3 y (5), and was a predictor of asthma development at age 7 y (6). The identification of mold as an important component of the environmental contribution to the asthma phenotype leads to questions about possible interventions to prevent and/or attenuate mold-related health effects. Two molds commonly identified in the homes of children enrolled in the Cincinnati Childhood Allergy and Air Pollution Study birth cohort were Aspergillus versicolor and Cladosporium cla-dosporioides (7). However, studies that examine the effects of these two molds on asthma are limited and largely descriptive. A study in Finland and another in New York City suggested that patients …