期刊
JOURNAL OF CLINICAL INVESTIGATION
卷 128, 期 8, 页码 3535-3545出版社
AMER SOC CLINICAL INVESTIGATION INC
DOI: 10.1172/JCI97065
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资金
- Deutsche Forschungsgemeinschaft [SFB-TR84 A5, C3/C6, SPP1656]
- Russian Science Foundation grant (IgA antibody generation) [17-74-20059]
- Charite Universitatsmedizin Berlin
- Swiss National Science Foundation
- Russian Science Foundation [17-74-20059] Funding Source: Russian Science Foundation
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.
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