Toll‐like receptor 2‐mediated modulation of growth and functions of regulatory T cells by oral streptococci. (18th February 2013)

• Record Type: Journal Article
• Authors: Saeki, A.; Segawa, T.; Abe, T.; Sugiyama, M.; Arimoto, T.; Hara, H.; Hasebe, A.; Ohtani, M.; Tanizume, N.; Ohuchi, M.; Kataoka, H.; Kawanami, M.; Yokoyama, A.; Shibata, K.
• Is Part Of: Molecular oral microbiology. Volume 28:Number 4(2013:Aug.)
• Page Start: 267
• Page End: 280
• Publication Date: 2013-02-18
• Subjects: Mouth -- Microbiology -- Periodicals; Respiratory infections -- Microbiology -- Periodicals; Mouth -- Diseases -- Immunological aspects -- Periodicals; 617.522
• DOI: 10.1111/omi.12023
• Languages: English
• ISSNs: 2041-1006

Abstract

<abstract abstract-type="main" id="omi12023-abs-0001"> <title>Summary</title> <p>This study was designed to determine whether oral streptococci modulate the growth and functions of regulatory T cells. Heat‐killed cells of wild‐type strains of <italic>Streptococcus gordonii</italic> and <italic>Streptococcus mutans</italic> induced the Toll‐like receptor 2 (TLR2) ‐mediated nuclear factor‐κB (NF‐κB) activation, but their lipoprotein‐deficient strains did not. Stimulation with these streptococci resulted in a significant increase in the frequency of CD4<sup>+</sup> CD25<sup>+</sup> Foxp3<sup>+</sup> regulatory T cells in splenocytes derived from both TLR2<sup>+/+</sup> and TLR2<sup>−/−</sup> mice, but the level of increase in TLR2<sup>+/+</sup> splenocytes was stronger than that in TLR2<sup>−/−</sup> splenocytes. Both strains of <italic>S. gordonii</italic> enhanced the proliferation of CD4<sup>+</sup> CD25<sup>+</sup> Foxp3<sup>+</sup> regulatory T cells isolated from TLR2<sup>+/+</sup> mice at the same level as those from TLR2<sup>−/−</sup> mice in an interleukin‐2‐independent manner. However, wild‐type and lipoprotein‐deficient strains of both streptococci did not enhance the suppressive activity of the isolated regulatory T cells <italic>in vitro</italic>, but rather inhibited it. TLR ligands also inhibited the suppressive activity of the regulatory T cells. Inhibition of the suppressive activity was recovered by the addition of anti‐IL‐6 antibody. Pretreatment of antigen‐presenting cells with the NF‐κB inhibitor BAY11‐7082 enhanced the suppressive activity of the regulatory T cells. These results suggested that interleukin‐6 produced by antigen‐presenting cells inhibits the suppressive activity of the regulatory T cells. Wild‐type strain, but not lipoprotein‐deficient strain, of <italic>S. gordonii</italic> reduced the frequency of CD4<sup>+</sup> CD25<sup>+</sup> Foxp3<sup>+</sup> regulatory T cells in the acute infection model, whereas both strains of <italic>S. gordonii</italic> increased it in the chronic infection model mice. Hence, this study suggests that oral streptococci are capable of modulating the growth and functions of regulatory T cells <italic>in vitro</italic> and <italic>in vivo</italic>.</p> </abstract>