PUBLICATION
CFTR Protects against Mycobacterium abscessus Infection by Fine-Tuning Host Oxidative Defenses
- Authors
- Bernut, A., Dupont, C., Ogryzko, N.V., Neyret, A., Herrmann, J.L., Floto, R.A., Renshaw, S.A., Kremer, L.
- ID
- ZDB-PUB-190214-10
- Date
- 2019
- Source
- Cell Reports 26: 1828-1840.e4 (Journal)
- Registered Authors
- Ogryzko, Nikolay, Renshaw, Steve A.
- Keywords
- CFTR, Mycobacterium abscessus, NADPH oxidase, cystic fibrosis, innate immunity, pathogenesis, zebrafish
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Cystic Fibrosis Transmembrane Conductance Regulator/immunology*
- Disease Models, Animal
- Mycobacterium Infections, Nontuberculous/immunology*
- Mycobacterium Infections, Nontuberculous/microbiology
- Mycobacterium Infections, Nontuberculous/prevention & control
- Mycobacterium abscessus/immunology*
- Mycobacterium abscessus/isolation & purification
- Oxidative Stress/immunology*
- Reactive Oxygen Species/immunology
- Zebrafish
- Zebrafish Proteins/immunology*
- PubMed
- 30759393 Full text @ Cell Rep.
Citation
Bernut, A., Dupont, C., Ogryzko, N.V., Neyret, A., Herrmann, J.L., Floto, R.A., Renshaw, S.A., Kremer, L. (2019) CFTR Protects against Mycobacterium abscessus Infection by Fine-Tuning Host Oxidative Defenses. Cell Reports. 26:1828-1840.e4.
Abstract
Infection by rapidly growing Mycobacterium abscessus is increasingly prevalent in cystic fibrosis (CF), a genetic disease caused by a defective CF transmembrane conductance regulator (CFTR). However, the potential link between a dysfunctional CFTR and vulnerability to M. abscessus infection remains unknown. Herein, we exploit a CFTR-depleted zebrafish model, recapitulating CF immuno-pathogenesis, to study the contribution of CFTR in innate immunity against M. abscessus infection. Loss of CFTR increases susceptibility to infection through impaired NADPH oxidase-dependent restriction of intracellular growth and reduced neutrophil chemotaxis, which together compromise granuloma formation and integrity. As a consequence, extracellular multiplication of M. abscessus expands rapidly, inducing abscess formation and causing lethal infections. Because these phenotypes are not observed with other mycobacteria, our findings highlight the crucial and specific role of CFTR in the immune control of M. abscessus by mounting effective oxidative responses.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping