Intrapulmonary targeting of RANTES/CCL5-responsive cells prevents chronic fungal asthma

Regulated upon activation in normal T cells, expressed, and secreted (RANTES)/CCL5 is abundantly expressed during atopic asthma, suggesting that it is an important mediator of this disease. The contribution of intrapulmonary RANTES/CCL5-sensitive cells during Aspergillus fumigatus-induced airway disease in mice was assessed in this study. The intranasal delivery of a chimeric protein comprised of RANTES/CCL5 and a truncated version of Pseudomonas exotoxin A (RANTES-PE38) significantly attenuated serum IgE, peribronchial eosinophilia, and airway hyperreactivity when it was administered from day 0 to 15 after intratracheal conidia challenge in A. fumigatus-sensitized mice but had little effect when delivered from day 15 to 30 after conidia challenge. Intranasal RANTES-PE38 treatment enhanced macrophage recruitment and accelerated fungal clearance in the lungs of RANTES-PE38-treated mice. These data reveal a major role for RANTES/CCL5 and its receptors in the development of fungal asthma yet reveal only a modest role in the chronic remodeling of the allergic airway in this disease.