Aspergillus fumigatus is a common fungus that everyone can come into contact with; in children with cystic fibrosis (CF), thicker mucus in the airways makes it easier for the fungus to remain in the lungs, increasing the likelihood that the immune system will develop antibodies against it (sensitization) in the early years of life. This sensitization can lead children to develop an allergy to the fungus, which can further degenerate into a more serious condition called Allergic Bronchopulmonary Aspergillosis, or ABPA. In this condition, IgE antibodies, which increase lung inflammation, are produced in greater numbers than IgG antibodies, which instead have an anti-inflammatory role.

The project, called IMMUNOASPECT, investigated new parameters for diagnosing Aspergillus sensitization in children, looking for ways to “divert” the immune system’s response in time before a chronic allergic reaction develops.

The researchers used peripheral blood samples from people with CF to measure key immunological parameters, i.e., the presence and concentration of different antibodies (IgE and IgG). They then isolated the fungus Aspergillus fumigatus from hypopharyngeal aspirates and analyzed all the fungal variants present. Finally, they correlated the results obtained. 

Lung organoids, i.e., miniature three-dimensional reproductions of the organ, and cell cultures that mimic lung tissue were used to understand how the lung epithelium reacts when the immune system has been “activated” against the fungus.
The researchers found that Aspergillus fumigatus can directly activate B cells of the immune system in the lungs. These cells, in turn, stimulate the production of an inflammatory cytokine called IL-17F, which increases inflammatory IgE levels and contributes to lung damage.
This process is mediated by the Dectin-1 receptor on B cells, which recognizes the fungus and triggers the response. Blocking IL-17F or Dectin-1 can reduce the allergic reaction, paving the way for possible therapeutic strategies.

The data obtained will need to be confirmed in vivo in an animal model of ABPA.
A further phase of this research will be to measure the effective doses of drugs, already used for other diseases in humans, capable of blocking IL-17F and Dectin-1 in a preclinical model of allergic aspergillosis. 

Taken together, the results could enable the development of an early diagnostic test for ABPA based on the measurement of IL-17F levels.