Antibiotic treatment-induced secondary IgA deficiency enhances susceptibility to Pseudomonas aeruginosa pneumonia.

Details

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Version: Final published version
License: Not specified
Serval ID
serval:BIB_D0B9A8A7C74B
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Antibiotic treatment-induced secondary IgA deficiency enhances susceptibility to Pseudomonas aeruginosa pneumonia.
Journal
The Journal of clinical investigation
Author(s)
Robak O.H., Heimesaat M.M., Kruglov A.A., Prepens S., Ninnemann J., Gutbier B., Reppe K., Hochrein H., Suter M., Kirschning C.J., Marathe V., Buer J., Hornef M.W., Schnare M., Schneider P., Witzenrath M., Bereswill S., Steinhoff U., Suttorp N., Sander L.E., Chaput C., Opitz B.
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Publication state
Published
Issued date
01/08/2018
Peer-reviewed
Oui
Volume
128
Number
8
Pages
3535-3545
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
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
Yes
Create date
27/08/2018 18:10
Last modification date
18/09/2019 6:10
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