Analysis of astrocytes against infection in Toxoplasma encephalitis

• Project/Area Number: 17K15680
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Oita University
• Principal Investigator: Hidano Shinya 大分大学, 医学部, 助教 (80516386)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: トキソプラズマ / アストロサイト / 樹状細胞 / TRAF6 / 脳炎 / CD40

Outline of Final Research Achievements

Toxoplasma gondii (T. gondii) is an obligate intracellular parasite that causes toxoplasmic encephalitis in immunocompromised patients. To clarify the role of the adaptor molecule TRAF6 at astrocytes in T.gondii infection, we infected mice lacking TRAF6 in astrocytes with T.gondii and found no change in mortality or the number of parasites in the brain compared to the WT mice. In contrast, dendritic cell-specific TRAF6-deficient (CKO) mice died 11 days after infection.
These results suggest that T. gondii in CKO mice were increased above the acceptable range of mouse tissues due to Insufficient IFN-γ levels immediately after infection because increasing of IFN-γ levels associated with T. gondii infection was delayed.

Academic Significance and Societal Importance of the Research Achievements

トキソプラズマ脳炎におけるアストロサイトのCD40、TLRシグナルがTRAF6に依存するのかアストロサイト特異的TRAF6欠損マウスの解析を行ったが、その病態に変化がなく、アストロサイトの抗原虫活性はTRAF6に依存しないことが明らかになった。一方で、樹状細胞特異的TRAF6欠損マウスでは、感染11日目に全例が死亡したことから、樹状細胞ではTRAF6シグナルが重要であることが示された。以上より、アストロサイトと樹状細胞ではそれぞれ異なるシグナル伝達により抗原虫活性が誘導されることが明らかとなり、標的の細胞に適した治療戦略を今後構築することが可能となると考えられた。

Research Products

• [Journal Article] Fucosyltransferase 8 plays a crucial role in the invasion and metastasis of pancreatic ductal adenocarcinoma. (2020)
  • Author(s): Tada K, Ohta M, Hidano S, Watanabe K, Hirashita T, Oshima Y, Fujnaga A, Nakanuma H, Masuda T, Endo Y, Takeuchi Y, Iwashita Y, Kobayashi T, Inomata M.
  • Journal Title: Surgery Today. Volume: Epub ahead of print Issue: 7 Pages: 129-134
  • DOI: 10.1007/s00595-019-01953-z
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Dysbiosis of the Gut Microbiota on the Inflammatory Background due to Lack of Suppressor of Cytokine Signalling-1 in Mice (2018)
  • Author(s): Gendo Y、Matsumoto T、Kamiyama N、Saechue B、Fukuda C、Dewayani A、Hidano S、Noguchi K、Sonoda A、Ozaki T、Sachi N、Hirose H、Ozaka S、Eshita Y、Mizukami K、Okimoto T、Kodama M、Yoshimatsu T、Nishida H、Daa T、Yamaoka Y、Murakami K、Kobayashi T
  • Journal Title: Inflammatory Intestinal Diseases Volume: 3 Issue: 3 Pages: 145-154
  • DOI: 10.1159/000495462
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Autoimmune sialadenitis is associated with the upregulation of chemokine/chemokine receptor pairs in T cell-specific TRAF6-deficient mice (2018)
  • Author(s): Noguchi Kaori、Kamiyama Naganori、Hidano Shinya、Gendo Yoshiko、Sonoda Akira、Ozaki Takashi、Hirose Haruna、Sachi Nozomi、Saechue Benjawan、Ozaka Sotaro、Eshita Yuki、Mizukami Kazuhiro、Kawano Kenji、Kobayashi Takashi
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 504 Issue: 1 Pages: 245-250
  • DOI: 10.1016/j.bbrc.2018.08.162
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Role of simvastatin in tumor lymphangiogenesis and lymph node metastasis (2018)
  • Author(s): Ji RC, Eshita Y, Kobayashi T, Hidano S, Kamiyama N, Onishi Y
  • Journal Title: Clin Exp Metastasis Volume: 35(8) Issue: 8 Pages: 785-796
  • DOI: 10.1007/s10585-018-9940-8
  • Peer Reviewed
• [Journal Article] Secondary Unconjugated Bile Acids Induce Hepatic Stellate Cell Activation (2018)
  • Author(s): Saga Kunihiro、Iwashita Yukio、Hidano Shinya、Aso Yuiko、Isaka Kenji、Kido Yasutoshi、Tada Kazuhiro、Takayama Hiroomi、Masuda Takashi、Hirashita Teijiro、Endo Yuichi、Ohta Masayuki、Kobayashi Takashi、Inomata Masafumi
  • Journal Title: International Journal of Molecular Sciences Volume: 19 Issue: 10 Pages: 3043-3043
  • DOI: 10.3390/ijms19103043
  • Peer Reviewed / Open Access
• [Journal Article] Oral administration of antibiotics results in fecal occult bleeding due to metabolic disorders and defective proliferation of the gut epithelial cell in mice (2018)
  • Author(s): Sonoda Akira、Kamiyama Naganori、Ozaka Sotaro、Gendo Yoshiko、Ozaki Takashi、Hirose Haruna、Noguchi Kaori、Saechue Benjawan、Sachi Nozomi、Sakai Kumiko、Mizukami Kazuhiro、Hidano Shinya、Murakami Kazunari、Kobayashi Takashi
  • Journal Title: Genes to Cells Volume: 23 Issue: 12 Pages: 1043-1055
  • DOI: 10.1111/gtc.12649
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Ess2 bridges transcriptional regulators and spliceosomal complexes via distinct interacting domains (2018)
  • Author(s): Ichiro Takada, Megumi Tsuchiya, Kaori Yanaka, Shinya, Hidano, Sayuri Takahashi, Takashi Kobayashi, Hidesato Ogawa, Sinichi Nakagawa, Makoto Makishima
  • Journal Title: Biochem Biophys Res Commun. Volume: 497 Issue: 2 Pages: 597-604
  • DOI: 10.1016/j.bbrc.2018.02.110
  • Peer Reviewed / Open Access
• [Journal Article] Development of intestinal M cells and follicle-associated epithelium is regulated by TRAF6-mediated NF-κB signaling. (2018)
  • Author(s): Kanaya T, Sakakibara S, Jinnohara T, Hachisuka M, Tachibana N, Hidano S, Kobayashi T, Kimura S, Iwanaga T, Nakagawa T, Katsuno T, Kato N, Akiyama T, Sato T, Williams IR, Ohno H.
  • Journal Title: J Exp Med. Volume: 5;215(2) Issue: 2 Pages: 501-519
  • DOI: 10.1084/jem.20160659
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Ribavirin inhibits Zika virus (ZIKV) replication inハvitro and suppresses viremia in ZIKV- infected STAT1-deficient mice. (2017)
  • Author(s): Kamiyama N, Soma R, Hidano S, Watanabe K, Umekita H, Fukuda C, Noguchi K, Gendo Y, Ozaki T, Sonoda A, Sachi N, Runtuwene LR, Miura Y, Matsubara E, Tajima S, Takasaki T, Eshita Y, Kobayashi T.
  • Journal Title: Antiviral Res. Volume: 146 Pages: 1-11
  • DOI: 10.1016/j.antiviral.2017.08.007
  • Peer Reviewed
• [Journal Article] アニサキス症の最近の知見と動向 (2017)
  • Author(s): 飛彈野真也、水上一弘、、佐知望美、神山長慶、小林隆志
  • Journal Title: 医学と薬学 Volume: 74巻 11号 Pages: 1387-1392
• [Journal Article] 蚊媒介性ウイルス疾患 (2017)
  • Author(s): 神山長慶、佐知望美、飛彈野真也、小林隆志
  • Journal Title: 臨床免疫・アレルギー科 Volume: 68 (1) Pages: 79-85
  • NAID: 40021263510
• [Presentation] 第97回日本生理学会大会 (2020)
  • Author(s): 神山長慶、Benjawan Saechue、Astri Dewayani、Thanyakorn Chalalai、飛彈野真也、佐知望美、小坂聡太郎、有木晋平、、曽我泰裕、後藤美月、小林隆志
  • Organizer: TRAF6 in T cells exacerbates the severity of experimental autoimmune encephalomyelitis by up-regulating CCR6 expression
• [Presentation] 第13回寄生虫感染免疫研究会 (2020)
  • Author(s): Shinya Hidano, Kazuhiro Mizukami, Naganori Kamiyama, Nozomi Sachi, Sotaro Ozaka, Kazunari Murakami and Takashi Kobayashi.
  • Organizer: Analysis of pathogenic mechanism in Anisakis infection
• [Presentation] ジカウイルスの細胞侵入能を規定するアミノ酸の同定および神経変性疾患の増悪メカニズムの解明 (2019)
  • Author(s): 神山長慶、Benjawan Saechue、Astri Dewayani、Thanyakorn Chalalai、Thanyakorn Chalalai、佐知望美、小坂聡太郎、有木晋平、曽我泰裕、後藤美月、飛彈野真也、小林隆志
  • Organizer: 第10回癌・炎症と抗酸化研究会
• [Presentation] 抗生物質や抗菌ペプチドによる腸内環境の変化が腸内細菌叢に及ぼす影響 (2019)
  • Author(s): 小坂聡太郎、有木晋平、園田光、Benjawan Saechue、Astri Dewayani、神山長慶、飛彈野真也、水上一弘、村上和成、小林隆志
  • Organizer: 第10回癌・炎症と抗酸化研究会
• [Presentation] 抗生物質起因性大腸炎モデルマウスに対する柴苓湯の保護効果の解明 (2019)
  • Author(s): 小坂聡太郎、有木晋平、園田光、佐知望美、後藤美月、曽我泰裕、広瀬晴奈、尾崎貴士、Benjawan Saechue、Astri Dewayani、神山長慶、飛彈野真也、水上一弘、村上和成、小林隆志
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] TRAF6 Regulation in TH9 Cell Responses to Tumor Growth (2019)
  • Author(s): Astri Dewayani, Naganori Kamiyama, Shinya Hidano, Takashi Ozaki, Akira Sonoda, Nozomi Sachi, Sotaro Ozaka, Shimpei Ariki, Benjawan Saechue, Takashi Kobayashi
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] Development of a portable reverse transcription loop-mediated isothermal amplification (RT-LAMP) system to detect the Chikungunya virus in a cost-effective manner (2019)
  • Author(s): B Saechue, N Kamiyama, Y Wang, C Fukuda, K Watanabe, Y Soga, M Goto, A Dewayani, S Ariki, H Hirose, S Ozaka, N Sachi, S Hidano, K Faisal, R Chowdhury, M Khan, F Hossain, P Ghosh, T Shirin, D Mondal, and T Kobayashi
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] "Zika virus African strain has higher entry ability to host cell than Asian strain, and exacerbates EAE" (2019)
  • Author(s): Naganori Kamiyama, Benjawan Saechue, Astri Dewayani, Shinya Hidano, Nozomi Sachi, Sotaro Ozaka, Shinpei Ariki, Yasuhiro Soga, Mizuki Goto, Ryosuke Suzuki ,Takashi Kobayashi
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] ゲノム編集マウスを用いたケモカインCCL20の腸管組織における生理的機能の解析 (2019)
  • Author(s): Nozomi Sachi, Chiaki Fukuda, Shinya Hidano, Naganori Kamiyama, Benjawan Saechue, Sotaro Ozaka, Astri Dewayani, Shimpei Ariki, Yasuhiro Soga, Mizuki Goto, Takashi Kobayashi
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] TRAF6を介した炎症シグナルを定量化するレポーターアッセイ系の樹立と炎症を抑制する新規分子の探索 (2019)
  • Author(s): "Yasuhiro Soga, Naganori Kamiyama, Benjawan Saechue, Astri Dewayani, Shinya Hidano, Nozomi Sachi, Sotaro Ozaka, Shinpei Ariki, Mizuki Goto, Takashi Kobayashi"
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] "白癬菌増殖抑制効果を有するわさびの機能分子の探索 " (2019)
  • Author(s): Mizuki Goto, Haruna Hirose, Naganori Kamiyama, Benjawan Saechue, Astri Dewayani, Shinya Hidano, Nozomi Sachi, Sotaro Ozaka, Shinpei Ariki, Yasuhiro Soga, Takashi Kobayashi
  • Organizer: 第42回日本分子生物学会年会
• [Presentation] "Zika virus African strain has higher cell entry ability than Asian strain, and exacerbates EAE" (2019)
  • Author(s): Shinya Hidano, Naganori Kamiyama, Nozomi Sachi, Sotaro Ozaka and Takashi Kobayashi.
  • Organizer: 第48回日本免疫学会総会
• [Presentation] TRAF6 deficiency in dendritic cells exacerbates the disease severity of Toxoplasma gondii infection in mice. (2019)
  • Author(s): Shinya Hidano, Naganori Kamiyama, Nozomi Sachi, Sotaro Ozaka and Takashi Kobayashi.
  • Organizer: 第48回日本免疫学会総会
• [Presentation] Role of Secretory leukocyte proteinase inhibitor (SLPI) in the pathogenesis of Inflammatory bowel disease (2019)
  • Author(s): Takashi Kobayashi, Sotaro Ozaka, Nozomi Sachi, Naganori Kamiyama, Shinya Hidano, Kiyoshi Takeda
  • Organizer: 第48回日本免疫学会総会
• [Presentation] TRAF6 in dendritic cells regulates innate immune control of Toxoplasma gondii. (2019)
  • Author(s): Shinya Hidano, Naganori Kamiyama, Nozomi Sachi, Sotaro Ozaka and Takashi Kobayashi
  • Organizer: 第47回免疫学会総会、学術集会
• [Presentation] TRAF6 in dendritic cells is required for resistance to Toxoplasma gondii infection. (2019)
  • Author(s): Shinya Hidano, Naganori Kamiyama, Nozomi Sachi, Sotaro Ozaka and Takashi Kobayashi
  • Organizer: 第12回寄生虫感染免疫研究会
• [Presentation] TRAF6 in dendritic cells regulates innate immune control of Toxoplasma gondii. (2019)
  • Author(s): Shinya Hidano, Naganori Kamiyama, Nozomi Sachi, Sotaro Ozaka, Astri Dewayani, Benjawan Saechue and Takashi Kobayashi
  • Organizer: 第88回日本寄生虫学会大会
• [Presentation] 劇症型アニサキス症における発症要因・メカニズムの解明 (2018)
  • Author(s): 飛彈野真也、水上一弘、財津純可、草野耀永、伊藤秀幸、佐知望美、神山長慶、村上和成、小林隆志
  • Organizer: 第26回分子寄生虫ワークショップ
• [Presentation] 胃アニサキス症の劇症化メカニズムの解明 (2018)
  • Author(s): 飛彈野真也、水上一弘、財津純可、草野耀永、伊藤秀幸、佐知望美、神山長慶、村上和成、小林隆志
  • Organizer: 第9回癌・炎症と抗酸化研究会
• [Presentation] Analysis of a fluorescent material in Anisakis larvae. (2018)
  • Author(s): Shinya Hidano, Tadashi Kondo, Kazuhiro Mizukami, Makoto Nakatani, Naganori Kamiyama, Nozomi Sachi, Kazunari Murakami, Osamu Hirose and Takashi Kobayashi
  • Organizer: 第11回寄生虫感染免疫研究会
• [Presentation] アストロサイトのSTAT1シグナルは、トキソプラズマ脳炎のコントロールに重要である。 (2017)
  • Author(s): Shinya Hidano, Christoph Konradt, Daniel P. Beiting, Lothar Hennighausen, Serge Fuchs, Anita A. Koshy, Naganori Kamiyama, Takashi Kobayashi and Christopher A Hunter.
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] トキソプラズマ脳炎におけるアストロサイトの感染防御機構の解明 (2017)
  • Author(s): 飛彈野真也, Christoph Konradt, Daniel P. Beiting, 神山長慶, 小林隆志、Christopher A Hunter.
  • Organizer: 第２５回分子寄生虫学ワークショップ
• [Presentation] アストロサイトのSTAT1シグナルは、トキソプラズマ脳炎のコントロールに重要である。 (2017)
  • Author(s): Shinya Hidano, Christoph Konradt, Daniel P. Beiting, Lothar Hennighausen, Serge Fuchs, Anita A. Koshy, Naganori Kamiyama, Takashi Kobayashi and Christopher A Hunter.
  • Organizer: 第86回 日本寄生虫学会大会
• [Presentation] 蛍光特性を示すアニサキス種の同定ならびに食品検査への応用 (2017)
  • Author(s): 近藤 雅，中谷 誠 , 飛彈野 真也 ，小林 隆志
  • Organizer: 第86回 日本寄生虫学会大会
• [Presentation] ヒト感染アニサキス症における種の同定と臨床症状との関連の検討 (2017)
  • Author(s): 水上一弘、飛彈野真也、伊藤秀幸、神山長慶、相馬 渉、阿部寿徳、勝田真琴、安部高志、永井敬之、後藤康彦、井上邦光、大場一生、卜部繁俊、吉田 亮、大仁田賢、安部高志、永井敬之、後藤康彦、井上邦光、大場一生、卜部繁俊、吉田 亮、大仁田賢、村上和成、小林隆志
  • Organizer: 第86回 日本寄生虫学会大会