Remission of chronic fungal asthma in the absence of CCR8

Background: Experimental studies have generated conflicting data regarding the role of CCR8 in antigen-driven allergic airway disease models, thereby dampening enthusiasm for further exploration of the targeting of CCR8 in asthma. Objective: Recent data show that the absence of CCR8 leads to a marked amplification of the innate immune response, and these data provided impetus for the current study, which addressed the role of this chemokine receptor in a model of fungal asthma. Methods: Wild-type (CCR8(+/+)) and CCR8-deficient (CCR8(-/-)) mice were sensitized to Aspergillus fumigatus antigens and challenged via intra-tracheal injection with live fungal conidia, and parameters of airway hyperresponsiveness, inflammation, and remodeling were examined. Results: At day 7 after conidia challenge in wild-type (CCR8(+/+)) and CCR8-deficient (CCR8(-/-)) mice sensitized to A fumigatus antigens, markedly less fungal material was present in the lungs of the CCR8(-/-) group compared with the CCR8(+/+) group. At day 14 after conidia challenge, all characteristic airway physiology inflammatory, and remodeling parameters of fungal asthma were significantly decreased or abolished in the CCR8(-/-) group relative to the CCR8(+/+) group. Conclusion: Together these data show that an enhanced innate immune response in the absence of CCR8 promotes the rapid clearance of fungal material from the lung, thereby facilitating the remission of fungal asthma. Clinical implications: This study shows that the clearance of fungal material from the lung was enhanced in the absence of CCR8, which suggests that this receptor may be an attractive target in fungal-allergic asthma and other fungal-associated pulmonary diseases.