Airway hyperresponsiveness, but not airway remodeling, is attenuated during chronic pulmonary allergic responses to Aspergillus in CCR4-/- mice

The role of CC chemokine receptor 4 (CCR4) during the development and maintenance of Th2-type allergic airway disease is controversial. In this study, we examined the role of CCR4 in the chronic allergic airway response to live Aspergillus fumigatus spores, or conidia, in A. fumigatus-sensitized mice. After the conidia challenge, mice lacking CCR4 (CCR4-/- mice) exhibited significantly increased numbers of airway neutrophils and macrophages, and conidia were more rapidly eliminated from these mice compared with control CCR4 wild-type (CCR4+/+) mice. Significant airway hyperresponsiveness to intravenous methacholine was observed at day 3 in CCR4-/- mice, whereas at days 7 and 30, airway hyperresponsiveness was attenuated in these mice compared with control mice. A major reduction in peribronchial and airway eosinophilia was observed in CCR4-/- mice at all times after conidia challenge in contrast to CCR4+/+ mice. Further, whole lung levels of interleukin (IL) 4 and IL-5 were significantly increased in CCR4-/- mice at day 3, whereas these Th2 cytokines and IL-13 were significantly decreased at day 30 in CCR4-/- mice compared with their wild-type counterparts. Peribronchial fibrosis and goblet cell hyperplasia were similar in both groups of mice throughout the course of this model. In summary, CCR4 modulates both innate and acquired immune responses associated with chronic fungal asthma.