Figure 3.

Unique features of fungal immune responses in the airway. Schematic of the unique features of fungi and their interactions with immune mechanisms in the murine airway. (A) Chitin in fungal cell walls triggers alternative activation of macrophages (M2 phenotype) and IL-4 expressing eosinophil and basophil responses, which can be inhibited by mammalian chitinases. (B) Fungal proteases signal through PAR-2 in the airway epithelium resulting in the release of IL-33, which consequently signals through ST2 to trigger IgE and ILC2 release of IL-5 and IL-13, promoting eosinophil recruitment to the airway. (C) β-glucan recognition through dectin-1 on macrophages results in the release of TNF-α, as well as a mixed Th1/Th2/Th17 response with the release of IL-4 and IL-13 by Th2 cells, IFN-γ by Th1 cells, IL-17A by Th17 cells, and IL-22 detected in unfractionated lung cells. (D) Extracellular vesicles (EV) trigger the release of cytokines IL-10, IL-12, TGF-β, and TNF-α by macrophages and dendritic cells. (E) A. fumigatus-induced allergic airway inflammation in mice induces IL-1R1 signalling and Th1 (IFN-γ, CXCL9, and CXCL10) and Th17 responses, with IL-17A promoting neutrophil infiltration. IL-1RA inhibits these pathways downstream of IL-1R1. Data presented from studies: (A) Reese et al., 2007; Van Dyken et al., 2011; (B) Bartemes et al., 2012; Snelgrove et al., 2014; Castanhinha et al., 2015; Hiraishi et al., 2018 (C) Gersuk et al., 2006; Lilly et al., 2012; (D) Vargas et al., 2015; and (E) Godwin et al., 2019.