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Molecules 2018, 23(8), 1979; https://doi.org/10.3390/molecules23081979

Phosphocholine-Modified Lipooligosaccharides of Haemophilus influenzae Inhibit ATP-Induced IL-1β Release by Pulmonary Epithelial Cells

1
Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, Justus-Liebig-University Giessen, German Center for Lung Research, 35392 Giessen, Germany
2
Department of Anesthesiology and Intensive Care Medicine, Justus-Liebig-University Giessen, 35392 Giessen, Germany
3
Institute of Anatomy and Cell Biology, Justus-Liebig-University Giessen, German Center for Lung Research, 35385 Giessen, Germany
4
Division of Chemistry, Department of Physics, Chemistry and Biology, Linköping University, S-58183 Linköping, Sweden
5
Department of Biology, University of Utah, Salt Lake City, UT 84112, USA
6
George E. Wahlen Veterans Affairs Medical Center, Salt Lake City, UT 84148, USA
7
Department of Psychiatry, University of Utah, Salt Lake City, UT 84108, USA
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 29 June 2018 / Revised: 19 July 2018 / Accepted: 27 July 2018 / Published: 8 August 2018
(This article belongs to the Special Issue Immunomodulatory Compounds)
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Abstract

Phosphocholine-modified bacterial cell wall components are virulence factors enabling immune evasion and permanent colonization of the mammalian host, by mechanisms that are poorly understood. Recently, we demonstrated that free phosphocholine (PC) and PC-modified lipooligosaccharides (PC-LOS) from Haemophilus influenzae, an opportunistic pathogen of the upper and lower airways, function as unconventional nicotinic agonists and efficiently inhibit the ATP-induced release of monocytic IL-1β. We hypothesize that H. influenzae PC-LOS exert similar effects on pulmonary epithelial cells and on the complex lung tissue. The human lung carcinoma-derived epithelial cell lines A549 and Calu-3 were primed with lipopolysaccharide from Escherichia coli followed by stimulation with ATP in the presence or absence of PC or PC-LOS or LOS devoid of PC. The involvement of nicotinic acetylcholine receptors was tested using specific antagonists. We demonstrate that PC and PC-LOS efficiently inhibit ATP-mediated IL-1β release by A549 and Calu-3 cells via nicotinic acetylcholine receptors containing subunits α7, α9, and/or α10. Primed precision-cut lung slices behaved similarly. We conclude that H. influenzae hijacked an endogenous anti-inflammatory cholinergic control mechanism of the lung to evade innate immune responses of the host. These findings may pave the way towards a host-centered antibiotic treatment of chronic airway infections with H. influenzae. View Full-Text
Keywords: A549; Calu-3; CHRNA7; CHRNA9; CHRNA10; immune evasion; inflammasome; lung; nicotinic acetylcholine receptor; phosphocholine-modification A549; Calu-3; CHRNA7; CHRNA9; CHRNA10; immune evasion; inflammasome; lung; nicotinic acetylcholine receptor; phosphocholine-modification
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Richter, K.; Koch, C.; Perniss, A.; Wolf, P.M.; Schweda, E.K.H.; Wichmann, S.; Wilker, S.; Magel, I.; Sander, M.; McIntosh, J.M.; Padberg, W.; Grau, V. Phosphocholine-Modified Lipooligosaccharides of Haemophilus influenzae Inhibit ATP-Induced IL-1β Release by Pulmonary Epithelial Cells. Molecules 2018, 23, 1979.

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