title: Effects of intestinal bacteria-derived p-cresyl sulfate on Th1-type immune response in vivo and in vitro.
abstract: 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-γ was suppressed by pCS. Further, pCS decreased the percentage of IFN-γ-producing Th1 cells. Our results suggest that intestinal bacteria-derived pCS suppressesTh1-type cellular immune responses.
authors.affiliation: Safety Research Department, Yakult Central Institute for Microbiological Research, 1796 Yaho, Kunitachi-Shi, Tokyo 186-8650, Japan. Electronic address: takahiro-shiba@yakult.co.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Shiba
authors.affiliation: Safety Research Department, Yakult Central Institute for Microbiological Research, 1796 Yaho, Kunitachi-Shi, Tokyo 186-8650, Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Kawakami
authors.affiliation: Safety Research Department, Yakult Central Institute for Microbiological Research, 1796 Yaho, Kunitachi-Shi, Tokyo 186-8650, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sasaki
authors.affiliation: Safety Research Department, Yakult Central Institute for Microbiological Research, 1796 Yaho, Kunitachi-Shi, Tokyo 186-8650, Japan.
authors.forename: Ikuyo
authors.initials: I
authors.lastname: Makino
authors.affiliation: Safety Research Department, Yakult Central Institute for Microbiological Research, 1796 Yaho, Kunitachi-Shi, Tokyo 186-8650, Japan.
authors.forename: Ikuo
authors.initials: I
authors.lastname: Kato
authors.affiliation: Safety Research Department, Yakult Central Institute for Microbiological Research, 1796 Yaho, Kunitachi-Shi, Tokyo 186-8650, Japan.
authors.forename: Toshihide
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Safety Research Department, Yakult Central Institute for Microbiological Research, 1796 Yaho, Kunitachi-Shi, Tokyo 186-8650, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Safety Research Department, Yakult Central Institute for Microbiological Research, 1796 Yaho, Kunitachi-Shi, Tokyo 186-8650, Japan.
authors.forename: Kimiyuki
authors.initials: K
authors.lastname: Kaneko
mesh_terms: D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003408:Cresols / Q000097:blood*; D003877:Dermatitis, Contact / Q000276:immunology / Q000473:pathology; D004139:Dinitrofluorobenzene / Q000009:adverse effects; D005260:Female; D054884:Host-Pathogen Interactions; D007107:Immune System / Q000382:microbiology*; D007111:Immunity, Cellular / Q000187:drug effects; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000382:microbiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D013463:Sulfuric Acid Esters / Q000097:blood*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology*; D014443:Tyrosine / Q000008:administration & dosage
chemical_list: D003408:Cresols; D013463:Sulfuric Acid Esters; D014443:Tyrosine; C408690:4-cresol sulfate; D007371:Interferon-gamma; D004139:Dinitrofluorobenzene
keywords: 2, 4-dinitrofluorobenzene; APC; CHS; CKD; Cellular immune response; DNFB; FITC; HRP; IFN-γ; Intestinal bacteria; KLH; PBS; PE; PMA; Th1 cell; Treg cell; allophycocyanin; chronic kidney disease; contact hypersensitivity; fluorescein isothiocyanate; horseradish peroxidase; keyhole limpet hemocyanin; mAb; monoclonal antibody; p-Cresol; p-Cresyl sulfate; p-cresyl sulfate; pCS; phorbol 12-myristate 13-acetate; phosphate-buffered saline; phycoerythrin; regulatory T cell