Beneficial effect of probiotics onPseudomonas aeruginosa–infected intestinal epithelial cells through inflammatory IL-8 and antimicrobial peptide human beta-defensin-2 modulation

Abstract

The human pathogen Pseudomonas aeruginosa can rapidly induce fatal sepsis, even in previously healthy infants or children treated with appropriate antibiotics. To reduce antibiotic overuse, exploring novel complementary therapies, such as probiotics that reportedly protect patients against P. aeruginosa infection, would be particularly beneficial. However, the major mechanism underlying the clinical effects is not completely understood. We thus aimed to investigate how probiotics affect IL-8 and human beta-defensin 2 (hBD-2) in P. aeruginosa–infected intestinal epithelial cells (IECs). We infected SW480 IECs with wild type PAO1 P. aeruginosa following probiotic treatment with Lactobacillus rhamnosus GG or Bifidobacterium longum spp. infantis S12, and analysed the mRNA expression and secreted protein of IL-8 and hBD-2, Akt signalling and NOD1 receptor protein expression. We observed that probiotics enhanced hBD-2 expression but suppressed IL-8 responses when administered before infection. They also enhanced P. aeruginosa–induced membranous NOD1 protein expression and Akt activation. The siRNA-mediated Akt or NOD1 knockdown counteracted P. aeruginosa–induced IL-8 or hBD-2 expression, indicating regulatory effects of these probiotics. In conclusion, these data suggest that probiotics exert reciprocal regulation of inflammation and antimicrobial peptides in P. aeruginosa–infected IECs and provide supporting evidence for applying probiotics to reduce antibiotic overuse.