Human-origin AR809 protects against immunosuppression in -induced pharyngitis Akt-mediated NF-κB and autophagy signaling pathways

Lactobacillus salivarius AR809 is a newly discovered probiotic strain from a healthy human pharynx and has 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 cytokines (tumor necrosis factor-α ( TNF-α ) and interleukin-1β ( IL-1β )), and induced macrophages to adopt the M2 phenotype. AR809 also attenuated S. aureus -induced phosphorylations of protein kinase B (Akt) and rapamycin (mTOR), and elevated the autophagic protein (light chain 3 from II ( LC3-II ) and Beclin-1 ) level. Furthermore, AR809 inhibited nuclear transcription factor kappa-B (NF-κB) activation by suppressing the nuclear translocation of 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 regulating 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. Lactobacillus salivarius AR809 is a newly discovered probiotic strain from a healthy human pharynx and has potential ability to adhere to the pharyngeal epithelium and inhibit Staphylococcus aureus ( S. aureus )-induced inflammatory response.