The role of CC chemokine receptor 5 (CCR5) and RANTES/CCL5 during chronic fungal asthma in mice.

Abstract

In the present study, we explored the role of CC chemokine receptor 5 (CCR5) in a murine model of chronic fungal asthma induced by an intrapulmonary challenge with Aspergillus fumigatus conidia (or spores). Airway hyperresponsiveness was significantly lower in A. fumigatus-sensitized mice lacking CCR5 (CCR5-/-) compared with similarly sensitized wild-type (CCR5+/+) control mice at days 2, 21, 30, and 40 after the conidia challenge. CCR5-/- mice exhibited significantly less peribronchial T-cell and eosinophil accumulation and airway-remodeling features, such as goblet cell hyperplasia and peribronchial fibrosis, compared with CCR5+/+ mice at these times after conidia. However, both groups of mice exhibited similar allergic airway disease at day 12 after the conidia challenge. In CCR5-/- mice at day 12, the allergic airway disease was associated with airway hyperresponsiveness, peribronchial allergic inflammation, and goblet cell hyperplasia. Immunoneutralization of RANTES/CCL5 in sensitized CCR5+/+ and CCR5-/- mice for 12 days after the conidia challenge significantly reduced the peribronchial inflammation and airway hyperresponsiveness in comparison with control wild-type and knockout mice at this time. These data demonstrate that functional CCR5 and RANTES/CCL5 are required for the persistence of chronic fungal asthma in mice.