CFTR Protects against Mycobacterium abscessus Infection by Fine-Tuning Host Oxidative Defenses.
Animals
Animals, Genetically Modified
Cystic Fibrosis Transmembrane Conductance Regulator
/ immunology
Disease Models, Animal
Mycobacterium Infections, Nontuberculous
/ immunology
Mycobacterium abscessus
/ immunology
Oxidative Stress
/ immunology
Reactive Oxygen Species
/ immunology
Zebrafish
Zebrafish Proteins
/ immunology
CFTR
Mycobacterium abscessus
NADPH oxidase
cystic fibrosis
innate immunity
pathogenesis
zebrafish
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
12 02 2019
12 02 2019
Historique:
received:
12
10
2018
revised:
17
12
2018
accepted:
17
01
2019
entrez:
14
2
2019
pubmed:
14
2
2019
medline:
22
4
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30759393
pii: S2211-1247(19)30100-7
doi: 10.1016/j.celrep.2019.01.071
pii:
doi:
Substances chimiques
CFTR protein, zebrafish
0
Reactive Oxygen Species
0
Zebrafish Proteins
0
Cystic Fibrosis Transmembrane Conductance Regulator
126880-72-6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1828-1840.e4Subventions
Organisme : Medical Research Council
ID : G0700091
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/M004864/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N02995X/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/L000830/1
Pays : United Kingdom
Informations de copyright
Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.