Saccharomyces cerevisiae β-glucan auspiciously improves the response of trained macrophages to severe P. aeruginosa infections.

Abstract

Abstract Objective P. aeruginosa (PA), the major pathogen of lung cystic fibrosis (CF), polarizes macrophages into hyperinflammatory tissue damaging phenotype. The main aim of this study was to verify whether training of macrophages with β-glucan (BG) might improve their response to P. aeruginosa infections. Methods To perform this task C57BL/6 mice sensitive to infections with P. aeruginosa were used. Peritoneal macrophages were trained with Saccharomyces cerevisiae BG and exposed to PA57, the bacterial strain isolated from the patient with severe lung CF. The release of cytokines and the expression of phenotypic markers of naïve and trained macrophages was measured. A quantitative proteomic approach was used for the characterization of proteome-wide changes in macrophages. Most importantly, the effect of trained macrophages in the air pouch model of PA57 infection was investigated. In all experiments the effect of trained macrophages was compared with that of naïve macrophages. Results Trained macrophages acquired a specific phenotype with mixed pro-inflammatory and pro-resolution characteristics, however they retained anti-bacterial properties. Transfer of trained macrophages into infected air pouches markedly ameliorated the course of infection. Bacterial growth and formation of biofilm were significantly suppressed. Conclusions Our study demonstrated that training of murine macrophages with S. cerevisiae β-glucan enhanced macrophage defense properties along with inhibition of secretion of some detrimental inflammatory agents. We suggest that training of macrophages with such β-glucan might be a new therapeutic strategy in P. aeruginosa infections, including CF.