Targeting Pseudomonas aeruginosa quorum sensing with sodium salicylate modulates immune responses in vitro and in vivo

利用水杨酸钠靶向铜绿假单胞菌群体感应调节体内和体外的免疫反应

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作者:Erik Gerner, Paula Milena Giraldo-Osorno, Anna Johansson Loo, Rininta Firdaus, Heithem Ben Amara, Maria Werthén, Anders Palmquist, Peter Thomsen, Omar Omar, Sofia Almqvist, Margarita Trobos

Aim

This study investigates how secreted factors from P. aeruginosa PAO1, cultured in the presence or absence of the QS inhibitor sodium salicylate (NaSa), influence host immune response. Material and

Conclusion

In conclusion, treating P. aeruginosa with NaSa reduces the production of virulence factors and modulates major immune events, such as promoting phagocytosis and cell migration, and decreasing the secretion of several pro-inflammatory cytokines.

Material and methods

In vitro, THP-1 macrophages and neutrophil-like HL-60 cells were used. In vivo, discs of titanium were implanted in a subcutaneous rat model with local administration of P. aeruginosa culture supernatants. The host immune response to virulence factors contained in culture supernatants (+/-NaSa) was characterized through cell viability, migration, phagocytosis, gene expression, cytokine secretion, and histology.

Methods

In vitro, THP-1 macrophages and neutrophil-like HL-60 cells were used. In vivo, discs of titanium were implanted in a subcutaneous rat model with local administration of P. aeruginosa culture supernatants. The host immune response to virulence factors contained in culture supernatants (+/-NaSa) was characterized through cell viability, migration, phagocytosis, gene expression, cytokine secretion, and histology.

Results

In vitro, P. aeruginosa supernatants from NaSa-containing cultures significantly increased THP-1 phagocytosis and HL-60 cell migration compared with untreated supernatants (-NaSa). Stimulation with NaSa-treated supernatants in vivo resulted in: (i) significantly increased immune cell infiltration and cell attachment to titanium discs; (ii) increased gene expression of IL-8, IL-10, ARG1, and iNOS, and (iii) increased GRO-α protein secretion and decreased IL-1β, IL-6, and IL-1α secretion, as compared with untreated supernatants.

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