Polymorphonuclear leukocytes restrict growth of <i>Pseudomonas aeruginosa</i> in the lungs of cystic fibrosis patients
- Authors:
-
-
Kragh, Kasper Nørskov
;
Close
0000-0002-7662-9118
Department of Immunology and Microbiology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Københavns Universitet - Alhede, Morten ;
- Jensen, Peter Østrup ;
- Moser, Claus Ernst ;
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Scheike, Thomas
;
Close0000-0002-2148-4740
Section of Biostatistics, Department of Public Health, Faculty of Health and Medical Sciences, Københavns Universitet - Jacobsen, Carsten S. ;
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Poulsen, Steen Seier
;
Close0000-0003-4419-4911
Endocrinology and Metabolism, Department of Biomedical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet - Eickhardt-Sørensen, Steffen Robert ;
- Trostrup, Hannah ;
- Christoffersen, Lars ;
- Hougen, Hans Petter ;
- Rickelt, Lars F. ;
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Kühl, Michael
;
Close0000-0002-1792-4790
Marine Biology, Department of Biology, Faculty of Science, Københavns Universitet -
Høiby, Niels
;
Close0000-0002-1347-725X
Department of Immunology and Microbiology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Københavns Universitet -
Bjarnsholt, Thomas
Close0000-0002-8003-7414
Department of Immunology and Microbiology, Department of Immunology and Microbiology, Faculty of Health and Medical Sciences, Københavns Universitet
-
Kragh, Kasper Nørskov
;
- DOI:
- 10.1128/IAI.01969-14
- Abstract:
- Cystic fibrosis (CF) patients have increased susceptibility to chronic lung infections by Pseudomonas aeruginosa, but the ecophysiology within the CF lung during infections is poorly understood. The aim of this study was to elucidate the in vivo growth physiology of P. aeruginosa within lungs of chronically infected CF patients. A novel, quantitative peptide nucleic acid (PNA) fluorescence in situ hybridization (PNA-FISH)-based method was used to estimate the in vivo growth rates of P. aeruginosa directly in lung tissue samples from CF patients and the growth rates of P. aeruginosa in infected lungs in a mouse model. The growth rate of P. aeruginosa within CF lungs did not correlate with the dimensions of bacterial aggregates but showed an inverse correlation to the concentration of polymorphonuclear leukocytes (PMNs) surrounding the bacteria. A growth-limiting effect on P. aeruginosa by PMNs was also observed in vitro, where this limitation was alleviated in the presence of the alternative electron acceptor nitrate. The finding that P. aeruginosa growth patterns correlate with the number of surrounding PMNs points to a bacteriostatic effect by PMNs via their strong O2 consumption, which slows the growth of P. aeruginosa in infected CF lungs. In support of this, the growth of P. aeruginosa was significantly higher in the respiratory airways than in the conducting airways of mice. These results indicate a complex host-pathogen interaction in chronic P. aeruginosa infection of the CF lung whereby PMNs slow the growth of the bacteria and render them less susceptible to antibiotic treatment while enabling them to persist by anaerobic respiration.
- Type:
- Journal article
- Language:
- English
- Published in:
- Infection and Immunity, 2014, Vol 82, Issue 11, p. 4477-4486
- Keywords:
- Adult; Animals; Biofilms; Cystic Fibrosis; Female; Humans; In Situ Hybridization, Fluorescence; Lung Diseases; Male; Mice; Mice, Inbred BALB C; Neutrophils; Peptide Nucleic Acids; Pseudomonas Infections; Pseudomonas aeruginosa; Journal Article; Research Support, Non-U.S. Gov't
- Main Research Area:
- Medical science
- Publication Status:
- Published
- Review type:
- Peer Review
- Submission year:
- 2014
- Scientific Level:
- Scientific
- ID:
- 269923990
