People with cystic fibrosis (CF) are often prone to chronic infections by antibiotic-resistant bacteria; bacteriophage (or phage)-based therapy, viruses that specifically attack bacteria, makes it possible to treat infections of even multi-resistant bacteria and could therefore be a useful option to eliminate them. However, although it is well established that phages are potent antimicrobial agents, little is known about their interaction with the human immune system, and this project set out to investigate this.

The researchers investigated the interaction of the DEV phage with the host immune system using different approaches and models, such as bronchial epithelial cells (CuFi) with a CFTR-F508del mutation, normal macrophages (cells involved in the immune response) and CFTR-inhibited macrophages.

Both normal and mutated/inhibited human cell models for CFTR were treated with the DEV phage to measure the levels of key cytokines, proteins that behave as indicators of the inflammatory state. Following DEV treatment, both bronchial epithelial cells and human macrophages showed a reduction in cytokine levels. 

The researchers demonstrated that the phage DEV has no inflammatory action but, on the contrary, presents an anti-inflammatory action. 
This finding is confirmed in zebrafish, normal or with loss of CFTR function, where a specific interaction of DEV with tissue macrophages was also demonstrated, which in turn reduces the recruitment of pro-inflammatory cells. Furthermore, in zebrafish, the researchers demonstrated how the DEV phage acts by modulating anti-inflammatory activity via tissue-specific macrophages which are also very important in the context of lung inflammation in CF.

From the data collected, phage therapy can be considered safe for the patient’s immune system. This is very important for the possible approval of this approach for human use and in a CF context, where the level of inflammation is always high.