Antibiotic treatment-induced secondary IgA deficiency enhances susceptibility to Pseudomonas aeruginosa pneumonia.
Détails
Télécharger: JCI97065.v3.pdf (2358.01 [Ko])
Etat: Public
Version: Final published version
Licence: Non spécifiée
Etat: Public
Version: Final published version
Licence: Non spécifiée
ID Serval
serval:BIB_D0B9A8A7C74B
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Antibiotic treatment-induced secondary IgA deficiency enhances susceptibility to Pseudomonas aeruginosa pneumonia.
Périodique
The Journal of clinical investigation
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Statut éditorial
Publié
Date de publication
01/08/2018
Peer-reviewed
Oui
Volume
128
Numéro
8
Pages
3535-3545
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Broad-spectrum antibiotics are widely used with patients in intensive care units (ICUs), many of whom develop hospital-acquired infections with Pseudomonas aeruginosa. Although preceding antimicrobial therapy is known as a major risk factor for P. aeruginosa-induced pneumonia, the underlying mechanisms remain incompletely understood. Here we demonstrate that depletion of the resident microbiota by broad-spectrum antibiotic treatment inhibited TLR-dependent production of a proliferation-inducing ligand (APRIL), resulting in a secondary IgA deficiency in the lung in mice and human ICU patients. Microbiota-dependent local IgA contributed to early antibacterial defense against P. aeruginosa. Consequently, P. aeruginosa-binding IgA purified from lamina propria culture or IgA hybridomas enhanced resistance of antibiotic-treated mice to P. aeruginosa infection after transnasal substitute. Our study provides a mechanistic explanation for the well-documented risk of P. aeruginosa infection following antimicrobial therapy, and we propose local administration of IgA as a novel prophylactic strategy.
Mots-clé
Animals, Anti-Bacterial Agents/pharmacology, Humans, Iatrogenic Disease, IgA Deficiency/drug therapy, IgA Deficiency/genetics, IgA Deficiency/immunology, IgA Deficiency/pathology, Immunoglobulin A/pharmacology, Mice, Mice, Knockout, Pneumonia, Bacterial/drug therapy, Pneumonia, Bacterial/genetics, Pneumonia, Bacterial/immunology, Pneumonia, Bacterial/pathology, Pseudomonas Infections/drug therapy, Pseudomonas Infections/genetics, Pseudomonas Infections/immunology, Pseudomonas Infections/pathology, Pseudomonas aeruginosa/immunology, Bacterial infections, Infectious disease
Pubmed
Web of science
Open Access
Oui
Création de la notice
27/08/2018 18:10
Dernière modification de la notice
21/11/2022 9:17