liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Pseudomonas aeruginosa lasI/rhlI quorum sensing genes promote phagocytosis and aquaporin 9 redistribution to the leading and trailing regions in macrophages
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Division of Microbiology and Molecular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
2015 (English)In: Frontiers in Microbiology, ISSN 1664-302X, E-ISSN 1664-302X, Vol. 6, no 915Article in journal (Refereed) Published
Abstract [en]

Pseudomonas aeruginosa controls production of its multiple virulence factors and biofilm development via the quorum sensing (QS) system. QS signals also interact with and affect the behavior of eukaryotic cells. Host water homeostasis and aquaporins (AQP) are essential during pathological conditions since they interfere with the cell cytoskeleton and signaling, and hereby affect cell morphology and functions. We investigated the contribution of F? aeruginosa QS genes lasl/rhIl to phagocytosis, cell morphology, AQP9 expression, and distribution in human macrophages, using immunoblotting, confocal, and nanoscale imaging. Wild type F? aeruginosa with a functional QS system was a more attractive prey for macrophages than the lasl/rhIl mutant lacking the production of QS molecules, 30-C-12-HSL, and C-4 -HSL, and associated virulence factors. The F? aeruginosa infections resulted in elevated AQP9 expression and relocalization to the leading and trailing regions in macrophages, increased cell area and length; bacteria with a functional QS system lasl/rhIl achieved stronger responses. We present evidence for a new role of water fluxes via AQP9 during bacteria macrophage interaction and for the QS system as an important stimulus in this process. These novel events in the interplay between F? aeruginosa and macrophages may influence on the outcome of infection, inflammation, and development of disease.

Place, publisher, year, edition, pages
FRONTIERS MEDIA SA , 2015. Vol. 6, no 915
Keyword [en]
host-bacteria relationship; quorum sensing; N-acylhomoserine lactone; innate immunity; macrophage; water homeostasis; aquaporin
National Category
Clinical Medicine
URN: urn:nbn:se:liu:diva-122056DOI: 10.3389/fmicb.2015.00915ISI: 000360626200001PubMedID: 26388857OAI: diva2:885411

Funding Agencies|Swedish Research Council [2010-3045]; European Science foundation (TraPPs Euromembrane project); Euro-BioImaging Proof-of Concept Studies; Magnus Bergvalls Foundation; Faculty of Health Sciences, Linkoping University

Available from: 2015-12-18 Created: 2015-10-19 Last updated: 2016-04-28
In thesis
1. Aquaporins in Infection and Inflammation
Open this publication in new window or tab >>Aquaporins in Infection and Inflammation
2016 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The ability of eukaryotic cells to change their shape and to migrate directionally is highly dependent on active volume regulation in cells building up tissues as well as in individual cells. Transmembrane fluxes of water via specialized water channels, called aquaporins (AQPs), facilitate the changes of volume and shape, which additionally require a complex interplay between the plasma membrane and the cytoskeleton. AQPs have been shown to be involved in the development of inflammatory processes and diseases. The aims of the studies underlying this thesis were to further elucidate the expression and function of AQPs in both bacterial and viral infections as well as in the inflammatory disease, microscopic colitis. For this, molecular techniques qPCR, immunoblotting and live, holographic, confocal and super-resolution imaging were used.

When cells of the innate immune system encounter pathogens they need to respond and prepare for migration and phagocytosis and do so through volume regulatory processes. The Gramnegative bacterium Pseudomonas aeruginosa utilizes a small molecule-based communication system, called quorum sensing (QS) to control the production of its virulence factors and biofilms. We found that P. aeruginosa with a complete QS system elicits a stronger phagocytic response in human blood-derived macrophages compared to its lasI-/rhlI- mutant lacking the production of the QS molecules N-butyryl-L-homoserine lactone (C4-HSL) and N-3-oxododecanoyl-L-homoserine lactone (3O-C12-HSL). Infection with P. aeruginosa further increases the expression of AQP9 and induces re-localisation of AQP9 to the front and trailing ends of macrophages. Moreover, the 3O-C12-HSL alone elevates the expression of AQP9, redistribute the water channel to the front and rear ends and increases the cell area and volume of macrophages. Both infection with the wild type P. aeruginosa and the treatment with 3OC12-HSL change the nano-structural architecture of the AQP9 distribution in macrophages.

Viruses use the intracellular machinery of the invaded cells to produce and assemble new viral bodies. Intracellular AQPs are localised in a membranes of cellular organelles to regulate their function and morphology. C3H10T1/2 fibroblasts transiently expressing green fluorescent protein (GFP)-AQP6 show a reduced expression of AQP6 after Hazara virus infection and an increased cell area. Overexpressing AQP6 in C3H10T1/2 cells reduces the infectivity of Hazara virus indicating that AQP6 expression has a protective role in virus infections.

Ion and water channels in the epithelial cell lining tightly regulate the water homeostasis. In microscopic colitis (MC), patients suffer from severe watery diarrhoeas. For the first time, we have shown that the expression of AQP1, 8 and 11 and the sodium/hydrogen exchanger NHE1 are reduced in colonic biopsies from MC patients compared to healthy control individuals. Following treatment with the glucocorticoid budesonide the patients experienced a rapid recovery and we observed a restored or increased expression of the AQPs and NHE1 during treatment, suggesting a role for AQPs in the diarrhoeal mechanisms in MC.

Taken together, this thesis provides new evidence on the importance of water homeostasis regulation through AQPs during infections and inflammation and opens up a door for further investigations of roles for AQPs in inflammatory processes.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2016. 58 p.
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1520
National Category
Public Health, Global Health, Social Medicine and Epidemiology Clinical Laboratory Medicine Cell and Molecular Biology
urn:nbn:se:liu:diva-127500 (URN)10.3384/diss.diva-127500 (DOI)978-91-7685-792-2 (Print) (ISBN)
Public defence
2016-06-02, Hasselqvistsalen, Campus US, Linköping, 09:00 (Swedish)
Available from: 2016-04-28 Created: 2016-04-28 Last updated: 2016-04-28Bibliographically approved

Open Access in DiVA

fulltext(2812 kB)49 downloads
File information
File name FULLTEXT01.pdfFile size 2812 kBChecksum SHA-512
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Holm, AngelikaKarlsson, ThommieVikström, Elena
By organisation
Division of Microbiology and Molecular MedicineFaculty of Medicine and Health Sciences
In the same journal
Frontiers in Microbiology
Clinical Medicine

Search outside of DiVA

GoogleGoogle Scholar
Total: 49 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 92 hits
ReferencesLink to record
Permanent link

Direct link