Abstract
Quorum sensing (QS) communication allows Pseudomonas aeruginosa to collectively control its population density and the production of biofilms and virulence factors. QS signal molecules, like N-3-oxo-dodecanoyl-L-homoserine lactone (3O-C12-HSL), can also affect the behavior of host cells, e.g., by modulating the chemotaxis, migration, and phagocytosis of human leukocytes. Moreover, host water homeostasis and water channels aquaporins (AQP) are critical for cell morphology and functions as AQP interact indirectly with the cell cytoskeleton and signaling cascades. Here, we investigated how P. aeruginosa 3O-C12-HSL affects cell morphology, area, volume and AQP9 expression and distribution in human primary macrophages, using quantitative PCR, immunoblotting, two- and three-dimensional live imaging, confocal and nanoscale imaging. Thus, 3O-C12-HSL enhanced cell volume and area and induced cell shape and protrusion fluctuations in macrophages, processes tentatively driven by fluxes of water across cell membrane through AQP9, the predominant AQP in macrophages. Moreover, 3O-C12-HSL upregulated the expression of AQP9 at both the protein and mRNA levels. This was accompanied with enhanced whole cell AQP9 fluorescent intensity and redistribution of AQP9 to the leading and trailing regions, in parallel with increased cell area in the macrophages. Finally, nanoscopy imaging provided details on AQP9 dynamics and architecture within the lamellipodial area of 3O-C12-HSL-stimulated cells. We suggest that these novel events in the interaction between P. aeruginosa and macrophage may have an impact on the effectiveness of innate immune cells to fight bacteria, and thereby resolve the early stages of infections and inflammations.
Highlights
The ability of a human cell to adjust and adapt its volume is vital for survival and proper functions
These live imaging data demonstrate that P. aeruginosa 3O-C12HSL signal molecules provoke quick expansion of cell area and changes in morphology in human macrophages and that these processes are driven by fluxes of water through AQP9
Cell volume and shape changes are strongly dependent on the transport of water through AQP, which is critical for their motility and phagocytosis in physiological conditions and in infection and inflammation (Lang et al, 1998; Hoffmann et al, 2009)
Summary
The ability of a human cell to adjust and adapt its volume is vital for survival and proper functions. The first one is comprised of the water-specific channels being permeable only to water; the second subfamily, aquaglyceroporins allows transport of both water and small uncharged molecules, like glycerol; the super-AQP, or subcellular-AQP (S-AQP) make up the third subgroup (Benga, 2012; Verkman, 2005). In patients with infectious endocarditis (Thuny et al, 2012), and systemic inflammatory response syndrome (Matsushima et al, 2014), the expression of AQP9 was elevated compared with healthy controls. Taken together, these data suggest an involvement of AQP9 in the inflammatory processes during bacterial infections
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