Ciszek-Lenda, M;
Strus, M;
Walczewska, M;
Majka, G;
Machul-Żwirbla, A;
Mikołajczyk, D;
Górska, S;
... Marcinkiewicz, J; + view all
(2019)
Pseudomonas aeruginosa biofilm is a potent inducer of phagocyte hyperinflammation.
Inflammation Research
10.1007/s00011-019-01227-x.
(In press).
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Abstract
OBJECTIVE: Pseudomonas aeruginosa effectively facilitate resistance to phagocyte killing by biofilm formation. However, the cross talk between biofilm components and phagocytes is still unclear. We hypothesize that a biofilm provides a concentrated extracellular source of LPS, DNA and exopolysaccharides (EPS), which polarize neighbouring phagocytes into an adverse hyperinflammatory state of activation. METHODS: We measured the release of a panel of mediators produced in vitro by murine neutrophils and macrophages exposed to various biofilm components of P. aeruginosa cultures. RESULTS: We found that conditioned media from a high biofilm-producing strain of P. aeruginosa, PAR5, accumulated high concentrations of extracellular bacterial LPS, DNA and EPS by 72 h. These conditioned media induced phagocytes to release a hyperinflammatory pattern of mediators, with enhanced levels of TNF-α, IL-6, IL12p40, PGE2 and NO. Moreover, the phagocytes also upregulated COX-2 and iNOS with no influence on the expression of arginase-1. CONCLUSIONS: Phagocytes exposed to biofilm microenvironment, called by us biofilm-associated neutrophils/macrophages (BANs/BAMs), display secretory properties similar to that of N1/M1-type phagocytes. These results suggest that in vivo high concentrations of LPS and DNA, trapped in biofilm by EPS, might convert infiltrating phagocytes into cells responsible for tissue injury without direct contact with bacteria and phagocytosis.
| Type: | Article |
|---|---|
| Title: | Pseudomonas aeruginosa biofilm is a potent inducer of phagocyte hyperinflammation |
| Location: | Switzerland |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1007/s00011-019-01227-x |
| Publisher version: | http://dx.doi.org/10.1007/s00011-019-01227-x |
| Language: | English |
| Additional information: | © The Author(s) 2019. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/). |
| Keywords: | Biofilm, DNA, Hyperinflammation, LPS, Neutrophils, P. aeruginosa |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10071110 |
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