Codonopsis pilosula polysaccharide attenuates cecal ligation and puncture sepsis via circuiting regulatory T cells in mice.

ABSTRACT

BACKGROUND: Codonopsis pilosula polysaccharide (CPPS) isolated from one of the Chinese herbs is known to have a variety of immunomodulatory activities. However, it is not clear whether CPPS can exert an effect on the immune functions of regulatory T cells (Tregs). This study was carried out to investigate the effect of CPPS on the immune function of peripheral blood Tregs in sepsis induced by cecal ligation and puncture (CLP). METHODOLOGY AND PRINCIPAL FINDINGS: BALB/c mice were randomly divided into five groups sham group, CLP group, CLP with CPPS (40, 100, and 250 mg/kg) treatment group, and they were killed on days 1, 2, 3, and 4 after CLP, respectively, with eight animals at each time point. Magnetic microbeads were used to isolate peripheral blood Tregs and CD4 T cells. Phenotypes of Tregs, such as Toll-like receptor 4 (TLR4) and Foxp3, were analyzed by flow cytometry, and coculture medium cytokines levels were determined with enzyme-linked immunosorbent assay. The levels of TLR4 and the expression of Foxp3 in the Treg from CLP group were markedly increased in comparison to the sham group. Administration of CPPS could significantly decrease the TLR4 level and inhibited the expression of Foxp3 on Tregs in sepsis mice. At the same time, proliferative activity and expression of interleukin 2 and interleukin 2Rα on CD4 T cells were restored. In contrast, anti-TLR4 antibody could block the effect of CPPS on Treg immune function. CONCLUSIONS: Codonopsis pilosula polysaccharide might suppress excessive Tregs, at least in part, via TLR4 signaling on Tregs and trigger a shift of TH2 to TH1 with activation of CD4 T cells in sepsis induced by CLP.