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.
- 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.
Keywords
- Bacterial infections
- Infectious disease
