Human-origin Lactobacillus salivarius AR809 protects against immunosuppression in S. aureus-induced pharyngitis via Akt mediated NF-κB and autophagy signaling pathways
Lactobacillus salivarius AR809 from healthy human pharynx, is a newly discovered probiotic strain possessing potential ability to adhere to the pharyngeal epithelium and inhibit Staphylococcus aureus (S. aureus)-induced inflammatory response. Pharyngeal spray administration of AR809 exhibited protective effects in a S. aureus-induced mouse model of pharyngitis. The inhibitory effect and underlying molecular mechanism of AR809 on S. aureus-stimulated pharyngitis were further investigated. AR809 significantly increased phagocytosis and bactericidal activity, reduced the production of inflammatory mediators (intracellular reactive oxygen species (ROS), prostaglandin E2 (PGE2), Cyclooxygenase-2 (COX-2), nitric oxide (NO), inducible NOS (iNOS)) and the expression of inflammatory cytokine (Tumor necrosis factor-a (TNF-a), Interleukin-1β (IL-1β)), and induced macrophages to adopt the M2 phenotype. AR809 also attenuated S. aureus-induced phosphorylations of protein kinase B (Akt), rapamycin (mTOR), and elevated the autophagic protein (light chain 3 from II (LC3-II), Beclin-1) level. Furthermore, AR809 inhibited nuclear transcription factor kappa-B (NF-κB) activation by suppressing the nuclear translocation of the NF-κB p65. Likewise, 740Y-P (a PI3K activator) decreased the anti-inflammatory effect of AR809 against S. aureus-induced inflammatory response, while AR809 treatments with wortmannin (a PI3K inhibitor) markedly reversed this inflammatory response. AR809 prevents S. aureus-induced pharyngeal inflammatory response, possibly by regulation of TLR/PI3K/Akt/mTOR signalling pathway-related autophagy and TLR/PI3K/Akt/IκB/NF-κB pathway activity, and therefore has potential for use in preventing pharyngitis and other inflammatory diseases.