Airway remodeling is absent in CCR1(-/-) mice during chronic fungal allergic airway disease

Asthmatic-like reactions characterized by elevated IgE, Th2 cytokines, C-C chemokines, eosinophilic inflammation, and persistent airway hyperresponsiv eness follow pulmonary exposure to the spores or conidia from Aspergillus f umigatus fungus in sensitized individuals. In addition to these features, s ubepithelial fibrosis and goblet cell hyperplasia characterizes fungal-indu ced allergic airway disease in mice. Because lung concentrations of macroph age inflammatory protein-1 alpha and RANTES were significantly elevated aft er A. fumigatus-sensitized mice received an intrapulmonary challenge with A . fumigatus spores or conidia, the present study addressed the role of thei r receptor, C-C chemokine receptor 1 (CCR1), in this model. A. fumigatus-se nsitized CCR1 wild-type (+/+) and CCR1 knockout (-/-) mice exhibited simila r increases in serum IgE and polymorphonuclear leukocyte numbers in the bro nchoalveolar lavage, Airway hyperresponsiveness was prominent in both group s of mice at 30 days after an intrapulmonary challenge with A. fumigatus sp ores or conidia, However, whole lung levels of IFN-gamma were significantly higher whereas IL-4, IL-13, and Th2-inducible chemokines such as C10, eota xin, and macrophage-derived chemokine were significantly lower in whole lun g samples from CCR1(-/-) mice compared with CCR1(+/+) mice at 30 days after the conidia challenge. Likewise, significantly fewer goblet cells and less subepithelial fibrosis were observed around large airways in CCR1-/- mice at the same time after the conidia challenge. Thus, these findings demonstr ate that CCR1 is a major contributor to the airway remodeling responses tha t arise from A. fumigatus-induced allergic airway disease.