Lung eosinophil recruitment in response to Aspergillus fumigatus is correlated with fungal cell wall composition and requires γδ T cells

Abstract

The differential recognition of fungal cell wall polysaccharides that program innate and adaptive immunity to the human opportunistic fungal pathogen Aspergillus fumigatus has been a focus of considerable interest. In a mouse model of fungal conidia aspiration, decreased relative levels of cell wall core carbohydrates β-1,3-glucan to chitin in A. fumigatus isolates and mutant strains were correlated with increased airway eosinophil recruitment. In addition, an increase in fungal surface chitin exposure induced by the β-1,3-glucan synthesis-targeting drug caspofungin was associated with increased murine airway eosinophil recruitment after a single challenge of conidia. The response to increased A. fumigatus chitin was associated with increased transcription of IL-17A after a single aspiration, although this cytokine was not required for eosinophil recruitment. Rather, both RAG1 and γδ T cells were required, suggesting that this subset of innate-like lymphocytes may be an important regulator of potentially detrimental type 2 immune responses to fungal inhalation and infection.