PMID- 28114402 OWN - NLM STAT- MEDLINE DCOM- 20170814 LR - 20181113 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 12 IP - 1 DP - 2017 TI - The Anti-Oxidant Ergothioneine Augments the Immunomodulatory Function of TLR Agonists by Direct Action on Macrophages. PG - e0169360 LID - 10.1371/journal.pone.0169360 [doi] LID - e0169360 AB - L-Ergothioneine (EGT) is a naturally-occurring amino acid which is characterized by its antioxidant property; yet, the physiological role of EGT has yet to be established. We investigated the immune-enhancing properties of EGT, and found that it acts as a potentiator of toll-like receptor (TLR) signaling. When mouse bone marrow-derived macrophages (BMDMs) were pretreated with EGT, TLR signal-mediated cytokine production was augmented in BMDMs. The results were reproducible with TLR2, 3, 4 and 7 agonists. In particular, IL-6 and IL-12p40 were elevated further by pretreatment with EGT in BMDMs, suggesting the induction of M1 polarization. In co-culture assay with OT-II CD4+ T cells and splenic F4/80+ macrophages, EGT significantly induced Th17 skewing in CD4+ T cells. Thus, EGT is an immune modifier as well as a redox controller under TLR stimulation that induces M1 macrophages and a Th17 shift in inflammation. FAU - Yoshida, Sumito AU - Yoshida S AD - Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo City, Japan. AD - Department of Pathology I, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo City, Japan. FAU - Shime, Hiroaki AU - Shime H AD - Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo City, Japan. FAU - Funami, Kenji AU - Funami K AD - Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo City, Japan. FAU - Takaki, Hiromi AU - Takaki H AD - Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo City, Japan. FAU - Matsumoto, Misako AU - Matsumoto M AD - Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo City, Japan. AD - Department of Pathology I, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo City, Japan. FAU - Kasahara, Masanori AU - Kasahara M AD - Department of Pathology I, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo City, Japan. FAU - Seya, Tsukasa AU - Seya T AD - Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo City, Japan. AD - Department of Pathology I, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo City, Japan. LA - eng PT - Journal Article DEP - 20170123 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Adjuvants, Immunologic) RN - 0 (Antioxidants) RN - 0 (Cytokines) RN - 0 (Reactive Oxygen Species) RN - 0 (Toll-Like Receptors) RN - BDZ3DQM98W (Ergothioneine) SB - IM MH - Adjuvants, Immunologic/*pharmacology MH - Animals MH - Antioxidants/*pharmacology MH - Cells, Cultured MH - Cytokines/biosynthesis MH - Ergothioneine/*pharmacology MH - Female MH - Macrophages/*drug effects/metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Transgenic MH - Reactive Oxygen Species/metabolism MH - Toll-Like Receptors/*agonists PMC - PMC5256913 COIS- The authors received funding from Three B Co., Inc., a commercial company, in the form of research materials for this study. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. EDAT- 2017/01/24 06:00 MHDA- 2017/08/15 06:00 PMCR- 2017/01/23 CRDT- 2017/01/24 06:00 PHST- 2016/07/07 00:00 [received] PHST- 2016/12/15 00:00 [accepted] PHST- 2017/01/24 06:00 [entrez] PHST- 2017/01/24 06:00 [pubmed] PHST- 2017/08/15 06:00 [medline] PHST- 2017/01/23 00:00 [pmc-release] AID - PONE-D-16-27125 [pii] AID - 10.1371/journal.pone.0169360 [doi] PST - epublish SO - PLoS One. 2017 Jan 23;12(1):e0169360. doi: 10.1371/journal.pone.0169360. eCollection 2017.