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N-Acylhomoserine lactones are potent neutrophil chemoattractants that act via calcium mobilization and actin remodeling
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Medical Microbiology. Linköping University, Faculty of Health Sciences.
2012 (English)In: Journal of Leukocyte Biology, ISSN 0741-5400, E-ISSN 1938-3673, Vol. 91, no 1, 15-26 p.Article in journal (Refereed) Published
Abstract [en]

In gram-negative bacteria, cell-cell communication based on HSL QS molecules is known to coordinate the production of virulence factors and biofilms. These bacterial signals can also modulate human immune cell behavior. Using a Transwell migration assay, we found that human primary neutrophils are strongly stimulated by 3O-C(12)-HSL and -C(10)-HSL but not C(4)-HSL in a concentration-dependent manner. Moreover, 3O-C(12)-HSL and -C(10)-HSL activate PLC gamma 1 but not -gamma 2, mobilize intracellular calcium, and up-regulate IP(3)R. These changes were paralleled by F-actin accumulation, primarily in the leading edge of neutrophils, as evidenced by phalloidin staining and confocal microscopy. F- and G-actin isolation and quantification by immunoblotting revealed that the F/G-actin ratio was increased significantly after treatment with all three HSLs. Furthemore, 3O-C(12)-HSL- and 3O-C(10)-HSL treatment resulted in phosphorylation of Rac1 and Cdc42. In contrast, C(4)-HSL had negligible influence on the phosphorylation status of PLC and Rac1/Cdc42 and failed to attract neutrophils and induce calcium release. The calcium inhibitor thapsigargin, which blocks ER calcium uptake, strongly prevented neutrophil migration toward 3O-C(12)-HSL and -C(10)-HSL. These findings show that the bacterial QS molecules 3O-C(12)-HSL and -C(10)-HSL may attract human neutrophils to the sites of bacterial infection and developing biofilms. Indeed, recognition of HSL QS signals by neutrophils may play a critical role in their recruitment during infections.

Place, publisher, year, edition, pages
Society for Leukocyte Biology , 2012. Vol. 91, no 1, 15-26 p.
Keyword [en]
quorum sensing, migration, Ca(2+), PLC, Rho-GTPases, cytoskeleton
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-74855DOI: 10.1189/jlb.0111034ISI: 000299168600004OAI: oai:DiVA.org:liu-74855DiVA: diva2:496549
Note
Funding Agencies|Swedish Research Council||European Science Foundation||King Gustaf V 80-Year Foundation||Faculty of Health Sciences, Linkoping University (Sweden)||Available from: 2012-02-10 Created: 2012-02-10 Last updated: 2017-12-07

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Karlsson, ThommieMagnusson, Karl-EricVikström, Elena

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