Wnt3a suppresses Pseudomonas aeruginosa-induced inflammation and promotes bacterial killing in macrophages.

Abstract

Pseudomonas aeruginosa (PA) is a common Gram-negative bacterium and can cause serious infections, including hospital-acquired pneumonia, suppurative bacterial keratitis and acute burn wound infection. The pathogenesis of PA infections is closely associated with excessive inflammatory responses and bacterial virulence factors. Wingless-type MMTV integration site family, member 3A (Wnt3a), an upstream mediator in the canonical Wnt signaling pathway, has been implicated as a regulator of inflammation. However, its role in PA-induced inflammation and bacterial clearance remains unknown. In the present study, the efficacy of Wnt3a conditioned media (Wnt3a-CM) was assessed using western blotting and immunofluorescence, which showed that β-catenin, a downstream molecule of Wnt3a, was upregulated and translocated to the nucleus following exposure to 50% Wnt3a-CM for 6 h. To explore the role of Wnt3a in PA-induced inflammation, the mRNA levels of pro-inflammatory cytokines and apoptosis in macrophages were measured using reverse transcription-quantitative polymerase chain reaction and flow cytometry, respectively. This indicated that Wnt3a suppressed inflammation by reducing the production of pro-inflammatory cytokines and by promoting apoptosis in macrophages. Furthermore, the mechanism of macrophage-mediated bacterial killing was investigated, and the results indicated that Wnt3a enhanced macrophage-mediated intracellular bacterial killing via the induction of the production of cathelicidin-related antimicrobial peptide and β-defensins 1. Taken together, the current study explored the role of Wnt3a in inflammation and bacterial invasion, which may provide an improved understanding of host resistance to PA infection.