Aspergillus fumigatus proteases, Asp f 5 and Asp f 13, are essential for airway inflammation and remodelling in a murine inhalation model.

[allergic bronchopulmonary aspergillosis]

In susceptible individuals , exposure to Aspergillus fumigatus can lead to the development of atopic lung diseases such as allergic bronchopulmonary aspergillosis (ABPA ) and severe asthma with fungal sensitization (SAFS ). Protease allergens including Asp f 5 and Asp f 13 from Aspergillus fumigatus , are thought to be important for initiation and progression of allergic asthma .To assess the importance of secreted protease allergens Asp f 5 (matrix metalloprotease ) and Asp f 13 (serine protease ) in Aspergillus fumigatus induced inflammation , airway hyperactivity , atopy and airway wall remodelling in a murine model following chronic exposure to secreted allergens . Methods : BALB /c mice were repeatedly intranasally dosed over the course of five weeks with culture filtrate from wild-type (WT ), Asp f 5 null (âˆ†5 ) or Asp f 13 null (âˆ†13 ) strains of Aspergillus fumigatus . Airway hyperreactivity was measured by non-invasive whole-body plethysmography , Th 2 response and airway inflammation by ELISA and cell counts , whilst airway remodelling was assessed by histological analysis .Parent WT and âˆ†5 culture filtrates showed high protease activity , whilst protease activity in âˆ†13 culture filtrate was low . Chronic intranasal exposure to the three different filtrates led to comparable airway hyperreactivity and Th 2 response . However , protease allergen deleted strains , in particular âˆ†13 culture filtrate , induced significantly less airway inflammation and remodelling compared to WT culture filtrate .Aspergillus fumigatus secreted allergen proteases , Asp f 5 and Asp f 13 , are important for recruitment of inflammatory cells and remodelling of the airways in this murine model . However , deletion of a single allergen protease fails to alleviate airway hyperreactivity and allergic immune response . Targeting protease activity of Aspergillus fumigatus in conditions such as SAFS or ABPA may have beneficial effects in preventing key aspects of airway pathology . This article is protected by copyright . All rights reserved .

Diseases
Validation

Diseases presenting "asthma" symptom

allergic bronchopulmonary aspergillosis

cutaneous mastocytosis

erdheim-chester disease

familial hypocalciuric hypercalcemia

lamellar ichthyosis

lymphangioleiomyomatosis

pendred syndrome

This symptom has already been validated