The researchers report the results of the experiments conducted on the in-vivo model of FC, the Zebrafish treated with bacteriophages. The ability of phages to act as anti-inflammatory agents even in the absence of bacterial infection was evaluated. To evaluate this activity, the researchers measured the expression of proinflammatory markers (interleukins) using molecular biology techniques such as quantitative PCR (qPCR). The signalling pathway of the receptors responsible for the recognition of pathogen molecules (Toll-Like Receptors; TLR) seems to exert the phages anti-inflammatory action. The researchers also report that the phages immunomodulatory effect is not dependent on the type of phage in the cocktail, in fact, the activity of each phage is comparable to that of the phage cocktail.
Furthermore, the researchers were able to establish that this activity is exerted by the protein component (capsid) of the phage and not by its DNA. Since the experimental model used, zebrafish has no lungs and does not perfectly recapitulate the mammalian system, the researchers also conducted experiments on human bronchial epithelial cell lines with the F508del mutation (CuFi-1 F508del). These in-vitro experiments are only preliminary and need further investigation to confirm those obtained in zebrafish. These experiments and further investigations may accelerate the use of bacteriophages as anti-inflammatory agents in the CF clinical setting.

Pubblications

• Cafora M, Brix A, Forti F et al. Phages as immunomodulators and their promising use as anti-inflammatory agents in a CFTR loss-of-function zebrafish model, Journal of Cystic Fibrosis, 2020 Dec 6;S1569-1993(20)30927-9
• Brix A, Cafora M, Aureli M et al. Animal Models to Translate Phage Therapy to Human Medicine, International Journal of Molecular Sciences, 2020 May 25;21(10):3715
• Cafora M, Foti F, Briani F et al., Phage Therapy Application to Counteract Pseudomonas aeruginosa Infection in Cystic Fibrosis Zebrafish Embryos, Journal of Visualized Experiments, 2020 May 12;(159)

Congress abstracts

• Cafora M, Forti F, Brix A et al. Potential action of phages as immunomodulators in cystic fibrosis, 43rd European Cystic Fibrosis Conference – 2020 (ECFC), virtual conference