Table 1.

Findings from selected mouse models of A. fumigatus airway sensitisation.

Mouse Strain	A. Fumigatus Delivery Method	Key Findings	Ref
A. fumigatus conidia-only models
C57BL6J	Intranasal delivery of 4 × 105 conidia (isolated from household dust samples), three times per week over 18 days.	Relative to fixed conidia, live conidia caused airway hyperreactivity, eosinophilia, elevated IL-4 and IL-17 levels. Both live and fixed conidia caused modest neutrophilia.	[90]
BALB/c	Nose-only aerosol challenge with approximately 1 × 105 conidia (strain B-5233/ATCC 13073) twice per week for 4 weeks.	Histology revealed persistence and germination of wild-type but not melanin-deficient conidia (∆alb1) 48 h post-final dose. Mice exposed to the wild-type but not ∆alb1 strain also displayed eosinophilia, neutrophilia Th2/Th17 sensitisation and evidence of subepithelial fibrosis and goblet cell hyperplasia by histology	[88]
C57BL6J	Intratracheal delivery of 2.5 × 106 conidia (strain Af293) embedded in agar beads once.	Non-invasive fungal growth in airway lumen coupled with galactomannan detection. Robust inflammation, including Th2, Th17 and neutrophilia. Severe airway remodelling by histology	[89]
C57BL6J	Intranasal delivery of 1 × 107 conidia (strain W72310 from ABPA patient or CEA10) seven times over 2 weeks.	W72310 but not CEA10 conidia persisted in the lung and could be detected as late as 28 days post-final exposure associated with eosinophilia, neutrophilia and Th2 sensitisation. Histology indicates subepithelial fibrosis and goblet cell hyperplasia in response to W72310.	[92]
C57BL6J	Intranasal delivery of 4 × 105 conidia (strain Af293), three times per week over 18 days	Evidence of Th2 sensitisation, increased subepithelial fibrosis and epithelial thickening coupled with increased Endothelin-1 levels.	[98]
Systemic sensitisation followed by A. fumigatus conidia and/or antigen
CBA/J	Systemic sensitisation by intraperitoneal and subcutaneous delivery of A. fumigatus antigen in Freund’s adjuvant, followed by a weekly challenge with A. fumigatus antigen for 3 weeks. In week 4, mice received an intratracheal dose of 5 × 106 conidia (strain 13073).	Relative to conidia alone, pre-sensitisation caused profound Th2 sensitisation, profound eosinophilia, neutrophilia and peribronchiolar inflammation. Analysis of histopathology showed that pre-sensitisation also caused goblet cell hyperplasia and subepithelial fibrosis.	[93]
BALB/c	Systemic sensitisation by intraperitoneal and subcutaneous delivery of A. fumigatus antigen in alum. After 2 weeks, mice received a weekly intranasal dose of A. fumigatus antigen for 3 weeks and 1 week later, an estimated 6.6 × 105 conidia (strain NIH 5233) were delivered by aerosol	Thickening of the epithelium, goblet cell hyperplasia and airway hyperreactivity persisted for at least 7 days post-final dose. Persistence of Th2 sensitisation and subepithelial fibrosis at the 35-day timepoint.	[94]
CBA/J	Systemic sensitisation by intraperitoneal and subcutaneous delivery of A. fumigatus antigen in Alum, followed by a weekly intranasal delivery of A. fumigatus antigen for 3 weeks. Finally, mice received a single intratracheal dose of 5 × 106 conidia (strain not specified).	Upregulation of IL-4 and IL-13. Neutralisation of IL-13, but not IL-4 significantly reduced airway hyperresponsiveness, collagen deposition and subepithelial fibrosis as shown by histology.	[97]
BALB/c	Systemic intraperitoneal sensitisation with alum and crude A. fumigatus extract (strain not specified) followed by intranasal delivery of crude extract on days 25–27. In a separate group, mice received crude extract eleven times over the course of 5 weeks.	Alp1/Asp f 13 immunoreactivity visible in the submucosa of A. fumigatus sensitised mice.	[99]
A. fumigatus extract or culture filtrate models
BALB/c and C57BL/6 derived genetically altered	Intranasal delivery of A. fumigatus extract (strain not specified), heat-inactivated extract or purified Alp1/Asp f 13, three times per week for 2 weeks.	Compared to mice receiving A. fumigatus extract or purified Alp1, those exposed to heat inactivated extract or Alp 1 showed diminished airway hyperreactivity, Th2 sensitisation, neutrophilia, peribronchiolar inflammation and goblet cell hyperplasia. Eosinophil-deficient and PAR2-deficient mice developed comparable inflammation, neutrophilia, Th2 sensitisation and goblet cell hyperplasia in response to Alp 1 to that found in wild-type mice.	[100]
BALB/c	Intranasal delivery of A. fumigatus sterilised and dialysed culture filtrate (CEA10 derived and protease allergen-deficient strains), twice per week for 4 weeks.	Neutrophilia, eosinophilia and Th2 sensitisation coupled with airway hyperreactivity and remodelling. Exposure to culture filtrates lacking protease allergens, Asp f 5 or Asp f 13, significantly reduced the extent of airway wall remodelling	[101]
C57BL6J	Intranasal delivery of A. fumigatus sterilised and dialysed culture filtrates (strain Af293), twice per week for 4 weeks.	Extensive inflammation and Th2 sensitisation in parallel with extensive subepithelial fibrosis. Endothelin-1 receptor antagonism prevented A. fumigatus-induced airway wall remodelling.	[98]