Differential influence of Streptococcus mitis on host response to metals in reconstructed human skin and oral mucosa.

BACKGROUND Skin and oral mucosa are continuously exposed to potential metal sensitizers whilst hosting abundant microbes which may influence the host response to sensitizers. This host response may also be influenced by the route of exposure i.e. skin or oral mucosa, due to their different immune properties. OBJECTIVE Determine how commensal Streptococcus mitis, influences the host response to nickel sulfate (sensitizer) and titanium(IV)-bis(ammonium-lactato)dihydroxide (questionable sensitizer) in reconstructed human skin (RHS) and gingiva (RHG). METHODS RHS/RHG were exposed to nickel or titanium, in the presence or absence of S. mitis for 24 hours. Histology, cytokine secretion and TLR expression was assessed. RESULTS S. mitis increased IL-6, CXCL8, CCL2, CCL5 and CCL20 secretion in RHS but not in RHG; co-application with nickel further increased cytokine secretion. In contrast, titanium suppressed S. mitis-induced cytokine secretion in RHS and had no influence on RHG. S. mitis and metals differentially regulated TLR1 and 4 in RHS, and predominantly TLR4 in RHG. CONCLUSION Co-exposure of S. mitis and nickel resulted in a more potent innate immune response in RHS than in RHG, while titanium remained inert. These results indicate the important influence of commensal microbes and the route of exposure on the host's response to metals. This article is protected by copyright. All rights reserved.