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

  • 2008-09
  • Infection and Immunity 76(9)
    • C. Cosseau
    • D. Devine
    • Edie M. Dullaghan
    • J. Gardy
    • Avinash Chikatamarla
    • S. Gellatly
    • Lorraine L. Yu
    • J. Pistolic
    • R. Falsafi
    • J. Tagg
    • R. Hancock

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 downregulate immune responses through the action on NF-kappaB 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 (Groalpha) 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, cytoskeletal 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 Groalpha secretion in response to flagellin. Immunosuppression was coincident with the inhibition of activation of the NF-kappaB 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.

Research Insights

SupplementHealth OutcomeEffect TypeEffect Size
Lactobacillus salivarius BLIS K12Reduced Baseline IL-8 SecretionBeneficial
Moderate
Lactobacillus salivarius BLIS K12Reduced Groalpha SecretionBeneficial
Moderate
Lactobacillus salivarius BLIS K12Reduced Induced Innate Immune ResponseBeneficial
Moderate
Streptococcus salivariusImproved Gut HomeostasisBeneficial
Large
Streptococcus salivariusReduced Activation of TLR4/NF-κB Signaling PathwayBeneficial
Moderate
Streptococcus salivariusReduced Baseline IL-8 SecretionBeneficial
Moderate
Streptococcus salivariusReduced Groalpha SecretionBeneficial
Moderate
Streptococcus salivariusReduced InflammationBeneficial
Large
Streptococcus salivarius BLIS K12Inhibited NF-κB ActivationBeneficial
Moderate
Streptococcus salivarius BLIS K12Reduced Induced Innate Immune ResponseBeneficial
Moderate
Streptococcus salivarius BLIS K12Reduced Pro-Inflammatory ResponseBeneficial
Moderate
Streptococcus salivarius K12Enhanced Host-Microbe BalanceBeneficial
Moderate
Streptococcus salivarius K12Reduced Apoptosis Induced by PathogensBeneficial
Moderate
Streptococcus salivarius K12Reduced Inflammation LevelsBeneficial
Moderate
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