Journal Article

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

Opitz, Bastian, Kruglov, Andrey A., Hochrein, Hubertus, Buer, Jan, Marathe, Veena, Bereswill, Stefan, Gutbier, Birgitt, Prepens, Sandra, Witzenrath, Martin, Heimesaat, Markus M., Suttorp, Norbert, Hornef, Mathias W., Sander, Leif E., Chaput, Catherine, Suter, Mark, Ninnemann, Justus, Schneider, Pascal, Robak, Oliver H., Kirschning, Carsten J., Steinhoff, Ulrich, Schnare, Markus, Reppe, Katrin

2018

Overview

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.

• Publisher: American Society for Clinical Investigation
• Subject: Animals / Anti-Bacterial Agents - pharmacology / Antibiotics / APRIL protein / Bacteria / Biomedical research / Care and treatment / Dendritic cells / Diagnosis / Dosage and administration / Drug resistance / Drug therapy / Health aspects / Humans / Iatrogenic Disease / IgA Deficiency - drug therapy / IgA Deficiency - genetics / IgA Deficiency - immunology / IgA Deficiency - pathology / Immunoglobulin A / Immunoglobulin A - pharmacology / Immunoglobulins / Intensive care / Intensive care units / Lamina propria / Lymphocytes / Management / Mice / Mice, Knockout / Microbiota / Microbiota (Symbiotic organisms) / Neutrophils / Nosocomial infections / Pathogens / Patients / Pneumonia / Pneumonia, Bacterial - drug therapy / Pneumonia, Bacterial - genetics / Pneumonia, Bacterial - immunology / Pneumonia, Bacterial - pathology / Pseudomonas aeruginosa / Pseudomonas aeruginosa - immunology / Pseudomonas aeruginosa infections / Pseudomonas Infections - drug therapy / Pseudomonas Infections - genetics / Pseudomonas Infections - immunology / Pseudomonas Infections - pathology / Risk factors / Viral infections