170 Polymorphonuclear leukocytes are suppressed by quorum sensing in a CF-mouse model of chronic Pseudomonas aeruginosa lung infection

ABSTRACT Pseudomonas aeruginosa causes a chronic infection in the lungs of cystic fibrosis (CF) patients by establishing an alginate-containing biofilm. The infection has been studied in several animal models; however, most of the models required artificial embedding of the bacteria. We present here a new pulmonary mouse model without artificial embedding. The model is based on a stable mucoid CF sputum isolate (NH57388A) with hyperproduction of alginate due to a deletion in mucA and functional N-acylhomoserine lactone (AHL)-based quorum-sensing systems. Chronic lung infection could be established in both CF mice (Cftr tmlUnc−/−) and BALB/c mice, as reflected by the detection of a high number of P. aeruginosa organisms in the lung homogenates at 7 days postinfection and alginate biofilms, surrounded by polymorphonuclear leukocytes in the alveoli. In comparison, both an AHL-producing nonmucoid revertant (NH57388C) from the mucoid isolate (NH57388A) and a nonmucoid isolate (NH57388B) deficient in AHL were almost cleared from the lungs of the mice. This model, in which P. aeruginosa is protected against the defense system of the lung by alginate, is similar to the clinical situation. Therefore, the mouse model provides an improved method for evaluating the interaction between mucoid P. aeruginosa, the host, and antibacterial therapy.

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Pseudomonas aeruginosa alginate is refractory to Th1 immune response and impedes host immune clearance in a mouse model of acute lung infection

Journal of Medical Microbiology ◽

10.1099/jmm.0.05122-0 ◽

2003 ◽

Vol 52 (9) ◽

pp. 731-740 ◽

Cited By ~ 49

Author(s):

Zhijun Song ◽

Hong Wu ◽

Oana Ciofu ◽

Kok-Fai Kong ◽

Niels Høiby ◽

...

Keyword(s):

Immune Response ◽

Pseudomonas Aeruginosa ◽

Mouse Model ◽

Lung Infection ◽

Immune Clearance ◽

Th1 Immune Response

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Effects of quorum-sensing on immunoglobulin G responses in a rat model of chronic lung infection with Pseudomonas aeruginosa

Microbes and Infection ◽

10.1016/j.micinf.2003.10.006 ◽

2004 ◽

Vol 6 (1) ◽

pp. 34-37 ◽

Cited By ~ 6

Author(s):

Hong Wu ◽

Zhijun Song ◽

Michael Givskov ◽

Niels Høiby

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Rat Model ◽

Immunoglobulin G ◽

Lung Infection ◽

Chronic Lung Infection

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Pseudomonas aeruginosa tolerance to tobramycin, hydrogen peroxide and polymorphonuclear leukocytes is quorum-sensing dependent

Microbiology ◽

10.1099/mic.0.27463-0 ◽

2005 ◽

Vol 151 (2) ◽

pp. 373-383 ◽

Cited By ~ 312

Author(s):

Thomas Bjarnsholt ◽

Peter Østrup Jensen ◽

Mette Burmølle ◽

Morten Hentzer ◽

Janus A. J. Haagensen ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Polymorphonuclear Leukocytes ◽

Present Report ◽

Cell Communication ◽

A Cell ◽

Opportunistic Human Pathogen ◽

Conventional Antibiotics

The opportunistic human pathogen Pseudomonas aeruginosa is the predominant micro-organism of chronic lung infections in cystic fibrosis (CF) patients. P. aeruginosa colonizes the CF lungs by forming biofilm structures in the alveoli. In the biofilm mode of growth the bacteria are highly tolerant to otherwise lethal doses of antibiotics and are protected from bactericidal activity of polymorphonuclear leukocytes (PMNs). P. aeruginosa controls the expression of many of its virulence factors by means of a cell–cell communication system termed quorum sensing (QS). In the present report it is demonstrated that biofilm bacteria in which QS is blocked either by mutation or by administration of QS inhibitory drugs are sensitive to treatment with tobramycin and H2O2, and are readily phagocytosed by PMNs, in contrast to bacteria with functional QS systems. In contrast to the wild-type, QS-deficient biofilms led to an immediate respiratory-burst activation of the PMNs in vitro. In vivo QS-deficient mutants provoked a higher degree of inflammation. It is suggested that quorum signals and QS-inhibitory drugs play direct and opposite roles in this process. Consequently, the faster and highly efficient clearance of QS-deficient bacteria in vivo is probably a two-sided phenomenon: down regulation of virulence and activation of the innate immune system. These data also suggest that a combination of the action of PMNs and QS inhibitors along with conventional antibiotics would eliminate the biofilm-forming bacteria before a chronic infection is established.

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Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice

Journal of Antimicrobial Chemotherapy ◽

10.1093/jac/dkh223 ◽

2004 ◽

Vol 53 (6) ◽

pp. 1054-1061 ◽

Cited By ~ 296

Author(s):

H. Wu

Keyword(s):

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Lung Infection ◽

Bacterial Clearance

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Quorum Sensing and Virulence of Pseudomonas aeruginosa during Lung Infection of Cystic Fibrosis Patients

PLoS ONE ◽

10.1371/journal.pone.0010115 ◽

2010 ◽

Vol 5 (4) ◽

pp. e10115 ◽

Cited By ~ 148

Author(s):

Thomas Bjarnsholt ◽

Peter Østrup Jensen ◽

Tim Holm Jakobsen ◽

Richard Phipps ◽

Anne Kirstine Nielsen ◽

...

Keyword(s):

Cystic Fibrosis ◽

Pseudomonas Aeruginosa ◽

Quorum Sensing ◽

Lung Infection

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The Effect of Treatment with Interleukin-1 and Tumor Necrosis Factor on Pseudomonas aeruginosa Lung Infection in a Granulocytopenic Mouse Model

Clinical Immunology and Immunopathology ◽

10.1006/clin.1994.1196 ◽

1994 ◽

Vol 73 (2) ◽

pp. 261-266 ◽

Cited By ~ 24

Author(s):

Claudia R. Amura ◽

Patricia A. Fontan ◽

Norberto Sanjuan ◽

Daniel O. Sordelli

Keyword(s):

Pseudomonas Aeruginosa ◽

Tumor Necrosis Factor ◽

Mouse Model ◽

Tumor Necrosis ◽

Interleukin 1 ◽

Lung Infection ◽

Effect Of Treatment ◽

Necrosis Factor

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NK cell-derived exosomes improved lung injury in mouse model of Pseudomonas aeruginosa lung infection

The Journal of Physiological Sciences ◽

10.1186/s12576-020-00776-9 ◽

2020 ◽

Vol 70 (1) ◽

Author(s):

Ruiqi Jia ◽

Kuili Cui ◽

Zhenkui Li ◽

Yuan Gao ◽

Bianfang Zhang ◽

...

Keyword(s):

Flow Cytometry ◽

Pseudomonas Aeruginosa ◽

Lung Injury ◽

Mouse Model ◽

Nk Cells ◽

Nk Cell ◽

Macrophage Polarization ◽

Lung Infection ◽

M2 Macrophage ◽

Lung Macrophage

Abstract Background Pseudomonas aeruginosa (PA) is one of the most common bacteria that causes lung infection in hospital. The aim of our study is to explore the role and action mechanism of NK cells in lung PA infection. Methods In this present study, 2.5 × 108 CFU/mouse PA was injected into murine trachea to make lung PA infection mouse model. Anti-asialo GM1 was used to inhibit NK cell. The percentage of NK cells was ensured by flow cytometry, and the M1- and M2-polarized macrophages were determined by flow cytometry, qRT-PCR, and ELISA assay. Besides, H&E staining was performed to ensure the pathological changes in lung tissues. Transmission electron microscopy and western blot were carried out to identify the exosome. Results Here, in the mouse model of PA lung infection, NK cell depletion caused M2 polarization of lung macrophage, and exacerbated PA-induced lung injury. Next, our data shown that M2 macrophage polarization was enhanced when the generation of NK cell-derived exosome was blocked in the co-culture system of NK cells and macrophages. Subsequently, we demonstrated that NK cells promoted M1 macrophage polarization both in PA-infected macrophage and the mouse model of PA lung infection, and attenuated lung injury through exosome. Conclusion Overall, our data proved that NK cell may improve PA-induced lung injury through promoting M1 lung macrophage polarization by secreting exosome. Our results provide a new idea for the treatment of PA lung infection.

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