Immune sensing of fungal cell wall carbohydrates programs immunity to A. fumigatus infection: role of γδ T cells. (MPF6P.662)

The human fungal pathogen Aspergillus fumigatus is associated with allergic sensitization and invasive infection in susceptible individuals. How the combined recognition of fungal molecular patterns programs host adaptive immunity is not well understood. Previously, we observed that fungal chitin promotes Th2-skewed immunity and eosinophil recruitment that proved detrimental to fungal clearance in invasive infection. In this study, we further characterized the role of early cytokine and effector cells in chitin derived eosinophil activation. We observed that single aspiration of a high-chitin isolate (Af5517) resulted in a marked increase in early transcription of IL-17A. Furthermore, eosinophil recruitment was not increased in RAG1-/- mice, suggesting that γδ T cells are required for early recognition of conidia-associated chitin. Although IL-17A was not required, the absence of γδ T cells (known to be potent sources of innate IL-17A) resulted in a significant decrease in eosinophil recruitment after single and multiple aspirations of Af5517. Also, fungal strains displaying chitin increased exposure or manipulating cell surface carbohydrate ratio by blockage of β-glucan recognition on receptor level resulted in increased airway eosinophil recruitment suggesting that relative high chitin/low β-glucan recognition leads to increased eosinophil recruitment and Th2 responses that are promoted by early responses of γδ T cells.