Journalartikel

Jahr der Veröffentlichung: 2018

Zeitschrift: Molecules

Bandnummer: 23

Heftnummer: 8

eISSN: 1420-3049

Open Access Status: Gold

DOI Link: https://doi.org/10.3390/molecules23081979

Verlag: MDPI

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-1 beta. 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-1 beta release by A549 and Calu-3 cells via nicotinic acetylcholine receptors containing subunits alpha 7, alpha 9, and/or alpha 10. 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.

Harvard-Zitierstil: Richter, K., Koch, C., Perniss, A., Wolf, P., Schweda, E., Wichmann, S., et al. (2018) Phosphocholine-Modified Lipooligosaccharides of Haemophilus influenzae Inhibit ATP-Induced IL-1β Release by Pulmonary Epithelial Cells, Molecules, 23(8), Article 1979. https://doi.org/10.3390/molecules23081979

APA-Zitierstil: Richter, K., Koch, C., Perniss, A., Wolf, P., Schweda, E., Wichmann, S., Wilker, S., Magel, I., Sander, M., McIntosh, J., Padberg, W., & Grau, V. (2018). Phosphocholine-Modified Lipooligosaccharides of Haemophilus influenzae Inhibit ATP-Induced IL-1β Release by Pulmonary Epithelial Cells. Molecules. 23(8), Article 1979. https://doi.org/10.3390/molecules23081979