Targeting quorum sensing with sodium salicylate modulates immune responses and .

Introduction: Chronic infections are a major clinical challenge in hard-to-heal wounds and implanted devices. is a common causative pathogen that produces numerous virulence factors. Due to the increasing problem of antibiotic resistance, new alternative treatment strategies are needed. Quorum sensing (QS) is a bacterial communication system that regulates virulence and dampens inflammation, promoting bacterial survival. QS inhibition is a potent strategy to reduce bacterial virulence and alleviate the negative impact on host immune response.

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

Material And Methods: , THP-1 macrophages and neutrophil-like HL-60 cells were used. , discs of titanium were implanted in a subcutaneous rat model with local administration of 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: , 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 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.

Conclusion: In conclusion, treating 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.