Schizophyllum commune Exopolysaccharides Reduce Salmonella Gut Epithelial Invasion and Activate Macrophages Towards...

Acute non-typhoidal salmonellosis (NTS) from non-typhoidal Salmonella remains a major cause of foodborne bacterial gastroenteritis, and non-antibiotic interventions are needed to combat multidrug-resistant NTS. Bioactive compounds from edible mushroom extracts have shown both direct and indirect antimicrobial activities on Salmonella. However, the variation in their antimicrobial activity could be due to several factors, including the extract's form and strain. This study investigated the ability of crude exopolysaccharides (EPs) produced by Schizophyllum commune CMU-01 to limit Salmonella infection in vitro. Agar well diffusion and liquid culture were used to determine the direct anti-Salmonella activity of S. commune EPs, while the gentamicin protection assay and qPCR in human gut epithelium (T84 cells) and murine macrophages (RAW264.7 cells) were used to investigate its indirect (immunomodulatory) activity. Our data reveal that S. commune EPs do not confer the direct antimicrobial property against Salmonella. However, its immunomodulatory activity in two important components of the gut innate defense (the gut epithelium and macrophages) against Salmonella infection has been demonstrated. S. commune EPs reduce Salmonella gut epithelial cell invasion and activate macrophages toward M1 (inflammatory phenotype) polarization, resulting in the reduction in intracellular Salmonella burdens. Alterations in proinflammatory and anti-inflammatory cytokine gene expressions were also detected in S. commune EPs-treated cells. These findings suggest that the host innate immune response to fungal exopolysaccharides derived from S. commune CMU-01 favors reducing Salmonella proliferation within host cells by altering the expression levels of proinflammatory cytokines.