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.
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
Figures
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Expression
Phenotype
Mutation and Transgenics
Human Disease / Model Data
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping
Errata and Notes