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The Commensal Streptococcus salivarius K12 Downregulates the Innate Immune Responses of Human Epithelial Cells and Promotes Host-Microbe Homeostasis

The Commensal Streptococcus salivarius K12 Downregulates the Innate Immune Responses of Human Epithelial Cells and Promotes Host-Microbe Homeostasis,1

The Commensal Streptococcus salivarius K12 Downregulates the Innate Immune Responses of Human Epithelial Cells and Promotes Host-Microbe Homeostasis   (Citations: 20)
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Streptococcus salivarius is an early colonizer of human oral and nasopharyngeal epithelia, and strain K12 has reported probiotic effects. An emerging paradigm indicates that commensal bacteria downregulate immune responses through the action on NF-B signaling pathways, but additional mechanisms underlying probiotic actions are not well understood. Our objective here was to identify host genes specifically targeted by K12 by comparing their responses with responses elicited by pathogens and to determine if S. salivarius modulates epithelial cell immune responses. RNA was extracted from human bronchial epithelial cells (16HBE14O- cells) cocultured with K12 or bacterial pathogens. cDNA was hybridized to a human 21K oligonucleotide-based array. Data were analyzed using ArrayPipe, InnateDB, PANTHER, and oPOSSUM. Interleukin 8 (IL-8) and growth-regulated oncogene alpha (Gro) secretion were determined by enzyme-linked immunosorbent assay. It was demonstrated that S. salivarius K12 specifically altered the expression of 565 host genes, particularly those involved in multiple innate defense pathways, general epithelial cell function and homeostasis, cytoskel- etal remodeling, cell development and migration, and signaling pathways. It inhibited baseline IL-8 secretion and IL-8 responses to LL-37, Pseudomonas aeruginosa, and flagellin in epithelial cells and attenuated Gro secretion in response to flagellin. Immunosuppression was coincident with the inhibition of activation of the NF-B pathway. Thus, the commensal and probiotic behaviors of S. salivarius K12 are proposed to be due to the organism (i) eliciting no proinflammatory response, (ii) stimulating an anti-inflammatory response, and (iii) modulating genes associated with adhesion to the epithelial layer and homeostasis. S. salivarius K12 might thereby ensure that it is tolerated by the host and maintained on the epithelial surface while actively protecting the host from inflammation and apoptosis induced by pathogens. Bacteria within the resident communities that colonize mu- cosal sites outnumber cells of the human body by 10-fold. Such populations are diverse as well as numerous; for example, around 700 taxa are normal inhabitants of the human mouth (1). Remarkably, these potentially overwhelming populations coexist with the host, with harmful effects occurring only if the immune status is altered or there is a loss of control of epithe- lial cell sensing and discriminatory systems. It is now generally accepted that this endogenous microflora possesses immuno- modulating capacities. Furthermore, some resident commensal bacteria have been shown to provide significant benefit to the host by blocking pathogen colonization and by influencing the normal development of cell structure and the immune system (5, 19, 29). This concept of beneficial bacteria has led to the advent of probiotics, the administration of viable microorgan- isms that confer health benefits to the host. Manipulation of the resident microflora using probiotics has become a realistic
Journal: Infection and Immunity - INFEC IMMUNITY , vol. 76, no. 9, pp. 4163-4175, 2008
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