PUBLICATION
Phages as immunomodulators and their promising use as anti-inflammatory agents in a cftr loss-of-function zebrafish model
- Authors
- Cafora, M., Brix, A., Forti, F., Loberto, N., Aureli, M., Briani, F., Pistocchi, A.
- ID
- ZDB-PUB-201212-13
- Date
- 2020
- Source
- Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society 20(6): 1046-1052 (Journal)
- Registered Authors
- Keywords
- Cystic fibrosis, Inflammation, Innate immunity, Phages, Zebrafish
- MeSH Terms
-
- Animals
- Anti-Inflammatory Agents/pharmacology*
- Bacteriophages*
- Cystic Fibrosis/drug therapy*
- Cystic Fibrosis/genetics*
- Cystic Fibrosis/immunology
- Immunity, Innate
- Immunologic Factors/pharmacology*
- Loss of Function Mutation*
- Pseudomonas Infections/drug therapy*
- Zebrafish
- PubMed
- 33298374 Full text @ J Cyst Fibros
Citation
Cafora, M., Brix, A., Forti, F., Loberto, N., Aureli, M., Briani, F., Pistocchi, A. (2020) Phages as immunomodulators and their promising use as anti-inflammatory agents in a cftr loss-of-function zebrafish model. Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society. 20(6):1046-1052.
Abstract
Cystic Fibrosis (CF), one of the most frequent hereditary diseases due to mutations in the CFTR gene, causes mortality in humans mainly due to infection in the respiratory system. However, besides the massive inflammatory response triggered by chronic bacterial infections, a constitutive pro-inflammatory state associated with the most common CFTR mutations has been reported in paediatric cases before the onset of bacterial colonization. In previous works we isolated and characterized a mix of virulent bacteriophages (phage cocktail) able to efficiently counteract Pseudomonas aeruginosa infection in a zebrafish model with cftr loss-of-function (LOF), but also showing anti-inflammatory effects in zebrafish embryos not infected by bacteria. On these premises, in this work we demonstrated the anti-inflammatory role of the phage cocktail both in the wild-type (WT) and hyper-inflamed cftr LOF zebrafish embryos in terms of reduction of pro-inflammatory markers. We also dissect that only the virion proteinaceous components, but not the phage DNA, are responsible for the immune-modulatory effect and that this action is elicited through the activation of the Toll-like Receptor (TLR) pathway. In the cftr LOF zebrafish embryos, we demonstrated that phages injection significantly reduces neutrophil migration following acute inflammatory induction. The elucidation of the molecular interaction between phages and the cells of vertebrate immune system might open new possibility in their manipulation for therapeutic benefits especially in diseases such as cystic fibrosis, characterized by chronic infection and inflammation.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping