Toll‐like receptor 2‐mediated modulation of growth and functions of regulatory T cells by oral streptococci. (18th February 2013) - Saeki, A.
Summary 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 Streptococcus gordonii and Streptococcus mutans 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+ CD25+ Foxp3+ regulatory T cells in splenocytes derived from both TLR2+/+ and TLR2−/− mice, but the level of increase in TLR2+/+ splenocytes was stronger than that in TLR2−/− splenocytes. Both strains of S. gordonii enhanced the proliferation of CD4+ CD25+ Foxp3+ regulatory T cells isolated from TLR2+/+ mice at the same level as those from TLR2−/− 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 in vitro, 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 S. gordonii reduced the frequency of CD4+ CD25+ Foxp3+ regulatory T cells in the acute infection model, whereas both strains of S. gordonii 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 in vitro and in vivo.