Effects of intestinal bacteria-derived p-cresyl sulfate on Th1-type immune response in vivo and in vitro

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• 作者：Takahiro Shiba ; Koji Kawakami ; Takashi Sasaki ; Ikuyo Makino ; Ikuo Kato ; Toshihide Kobayashi ; Kazumi Uchida ; Kimiyuki Kaneko
• 关键词：APC ; allophycocyanin ; CHS ; contact hypersensitivity ; CKD ; chronic kidney disease ; DNFB ; 2 ; 4-dinitrofluorobenzene ; FITC ; fluorescein isothiocyanate ; HRP ; horseradish peroxidase ; KLH ; keyhole limpet hemocyanin ; mAb ; monoclonal antibody ; PBS ; phosphate-buffered saline ; pCS ; p-cresyl sulfate ; PE ; phycoerythrin ; PMA ; phorbol 12-myristate 13-acetate ; Treg cell ; regulatory T cell
• 刊名：Toxicology and Applied Pharmacology
• 出版年：15 January, 2014
• 年：2014
• 卷：274
• 期：2
• 页码：191-199
• 全文大小：1131 K

文摘

Protein fermentation by intestinal bacteria generates various compounds that are not synthesized by their hosts. An example is p-cresol, which is produced from tyrosine. Patients with chronic kidney disease (CKD) accumulate high concentrations of intestinal bacteria-derived p-cresyl sulfate (pCS), which is the major metabolite of p-cresol, in their blood, and this accumulation contributes to certain CKD-associated disorders. Immune dysfunction is a CKD-associated disorder that frequently contributes to infectious diseases among CKD patients. Although some studies imply pCS as an etiological factor, the relation between pCS and immune systems is poorly understood. In the present study, we investigated the immunological effects of pCS derived from intestinal bacteria in mice. For this purpose, we fed mice a tyrosine-rich diet that causes the accumulation of pCS in their blood. The mice were shown to exhibit decreased Th1-driven 2, 4-dinitrofluorobenzene-induced contact hypersensitivity response. The concentration of pCS in blood was negatively correlated with the degree of the contact hypersensitivity response. In contrast, the T cell-dependent antibody response was not influenced by the accumulated pCS. We also examined the in vitro cytokine responses by T cells in the presence of pCS. The production of IFN-纬 was suppressed by pCS. Further, pCS decreased the percentage of IFN-纬-producing Th1 cells. Our results suggest that intestinal bacteria-derived pCS suppressesTh1-type cellular immune responses.