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This host response may also be influenced by the route of exposure that is skin or oral mucosa, due to their different immune properties.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>Determine how commensal<jats:italic>Streptococcus mitis<\/jats:italic>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).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>RHS\/RHG was exposed to nickel or titanium, in the presence or absence of<jats:italic>S. mitis<\/jats:italic>for 24\u2009hours. Histology, cytokine secretion, and Toll\u2010like receptors (TLRs) expression were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>S. mitis<\/jats:italic>increased interleukin (IL)\u20106, CXCL8, CCL2, CCL5, and CCL20 secretion in RHS but not in RHG; co\u2010application with nickel further increased cytokine secretion. In contrast, titanium suppressed<jats:italic>S. mitis<\/jats:italic>\u2013induced cytokine secretion in RHS and had no influence on RHG.<jats:italic>S. mitis<\/jats:italic>and metals differentially regulated TLR1 and TLR4 in RHS, and predominantly TLR4 in RHG.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Co\u2010exposure of<jats:italic>S. mitis<\/jats:italic>and nickel resulted in a more potent innate immune response in RHS than in RHG, whereas titanium remained inert. These results indicate the important influence of commensal microbes and the route of exposure on the host's response to metals.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cod.13668","type":"journal-article","created":{"date-parts":[[2020,7,17]],"date-time":"2020-07-17T05:47:08Z","timestamp":1594964828000},"page":"347-360","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Differential influence of<i>Streptococcus mitis<\/i>on host response to metals in reconstructed human skin and oral mucosa"],"prefix":"10.1111","volume":"83","author":[{"given":"Lin","family":"Shang","sequence":"first","affiliation":[{"name":"Department of Preventive Dentistry, Academic Centre for Dentistry Amsterdam (ACTA) University of Amsterdam and Vrije Universiteit Amsterdam Amsterdam The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongmei","family":"Deng","sequence":"additional","affiliation":[{"name":"Department 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