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Infect. Immun. doi:10.1128/IAI.00188-08
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

The commensal Streptococcus salivarius K12 down-regulates the innate immune responses of human epithelial cells and promotes host-microbe homeostasis

Centre for Microbial Diseases and Immunity Research, University of British Columbia, Vancouver, Canada; Department of Oral Biology, Leeds Dental Institute, University of Leeds, UK; Inimex Pharmaceuticals, Canada; Department of Microbiology and Immunology, University of Otago, New Zealand

^* To whom correspondence should be addressed. Email: bob{at}cmdr.ubc.ca.

	Abstract

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 down-regulate immune responses through action on NF-B signalling pathways but additional mechanisms underlying probiotic actions are not well understood. Our objective here was to identify host genes specifically targeted by K12 by comparison with responses elicited by pathogens and to determine if S. salivarius modulated epithelial cell immune responses. RNA was extracted from human bronchial epithelial cells (16HBE14O-) co-cultured with K12 or bacterial pathogens. cDNA was hybridised to a 21K human oligo-based array. Data were analysed using ArrayPipe, InnateDB, PANTHER, and oPOSSUM. IL8 and Gro secretion were determined by ELISA. It was demonstrated that S. salivarius K12 specifically altered the expression of 572 host genes, particularly those involved in multiple innate defence pathways, general epithelial cell function and homeostasis, cytoskeletal remodelling, cell development and migration, and signalling pathways. It inhibited baseline IL8 secretion and IL8 responses to LL-37, P. aeruginosa and flagellin in epithelial cells, and attenuated Gro secretion in response to flagellin. Immunosuppression was coincident with inhibition of activation of the NF-B pathway. Thus the commensal and probiotic behaviours of S. salivarius K12 are proposed to be due to the organism: (a) eliciting no pro-inflammatory response; (b) stimulating an anti-inflammatory response; and (c) 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.