Study on the balance between protective and regulatory immune responses that determine the pathogenesis of malaria infection in the endemic region of Kenya

• Project/Area Number: 15H05277
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 海外学術
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Nagasaki University
• Principal Investigator: YUI Katsuyuki 長崎大学, 医歯薬学総合研究科(医学系), 教授 (90274638)
• Co-Investigator(Kenkyū-buntansha): 木村 大輔 長崎大学, 医歯薬学総合研究科(医学系), 講師 (50423637) ; 濱野 真二郎 長崎大学, 熱帯医学研究所, 教授 (70294915)
• Co-Investigator(Renkei-kenkyūsha): KANEKO Osamu 長崎大学, 熱帯医学研究所, 教授 (50325370)
• Research Collaborator: KIJOGI Caroline
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000); Fiscal Year 2017: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2015: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
• Keywords: Malaria / T cells / Cytokine / Africa / マラリア / 免疫応答 / T細胞 / サイトカイン / 無症状 / 免疫抑制 / ケニア / 免疫学 / 末梢血 / 住血吸虫 / 感染症 / 寄生虫 / 原虫 / アフリカ / フィールド / 免疫 / 白血球

Outline of Final Research Achievements

Individuals living in malaria endemic areas become clinically immune after multiple re-infections over time and remain infected without apparent symptoms. However, it is unclear how such a balanced status of the infection and immunity is maintained.
We conducted a cross-sectional study of the immune responses in asymptomatic school children living in an endemic region of Plasmodium falciparum infections in Kenya. The production of cytokines by peripheral blood mononuclear cells in response to P. falciparum crude antigens exhibited strong heterogeneity among children. In addition, production of IL-2 in response to T-cell receptor stimulation was reduced in children with positive as compared to negative P. falciparum findings. These data suggest that T cell immune responses are generally suppressed among asymptomatic infected children living in the endemic region of P. falciparum,

Research Products

• [Int'l Joint Research] Kenya Medical Research Institute(ケニア)
• [Int'l Joint Research] Kenya Medical Research Institute(ケニア)
• [Journal Article] Modulation of immune responses by Plasmodium falciparum infection in asymptomatic children living in the endemic region of Mbita, western Kenya (2018)
  • Author(s): Kijogi Caroline、Kimura Daisuke、Bao Lam Quoc、Nakamura Risa、Chadeka Evans Asena、Cheruiyot Ngetich Benard、Bahati Felix、Yahata Kazuhide、Kaneko Osamu、Njenga Sammy M.、Ichinose Yoshio、Hamano Shinjiro、Yui Katsuyuki
  • Journal Title: Parasitology International Volume: 67 Issue: 3 Pages: 284-293
  • DOI: 10.1016/j.parint.2018.01.001
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Nonspecific CD8+ T Cells and Dendritic Cells/Macrophages Participate in Formation of CD8+ T Cell-Mediated Clusters against Malaria Liver-Stage Infection (2018)
  • Author(s): Akbari Masoud、Kimura Kazumi、Bayarsaikhan Ganchimeg、Kimura Daisuke、Miyakoda Mana、Juriasingani Smriti、Yuda Masao、Amino Rogerio、Yui Katsuyuki
  • Journal Title: Infection and Immunity Volume: 86 Issue: 4
  • DOI: 10.1128/iai.00717-17
  • NAID: 120006988034
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] SIRPα+dendritic cells regulate homeostasis of fibroblastic reticular cells via TNF receptor ligands in the adult spleen (2017)
  • Author(s): Saito Yasuyuki、Respatika Datu、Komori Satomi、Washio Ken、Nishimura Taichi、Kotani Takenori、Murata Yoji、Okazawa Hideki、Ohnishi Hiroshi、Kaneko Yoriaki、Yui Katsuyuki、Yasutomo Koji、Nishigori Chikako、Nojima Yoshihisa、Matozaki Takashi
  • Journal Title: Proceedings of the National Academy of Sciences Volume: 114 Issue: 47
  • DOI: 10.1073/pnas.1711345114
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Activation and exhaustion of antigen-specific CD8+ T cells occur in different splenic compartments during infection with Plasmodium berghei. (2017)
  • Author(s): 1.Bayarsaikhan G, Miyakoda M, Yamamoto K, Kimura D, Akbari M, Yuda M, Yui K
  • Journal Title: Parasitol Int Volume: 66(3) Issue: 3 Pages: 227-235
  • DOI: 10.1016/j.parint.2017.01.022
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Intravital imaging of the immune responses during liver-stage malaria infection: An improved approach for fixing the liver. (2016)
  • Author(s): Akbari M, Kimura K, Houts JT, Yui K.
  • Journal Title: Parasitol Int. Volume: 印刷中 Issue: 5 Pages: 0-0
  • DOI: 10.1016/j.parint.2016.02.011
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Interleukin-27-Producing CD4(+) T Cells Regulate Protective Immunity during Malaria Parasite Infection. (2016)
  • Author(s): Kimura D, Miyakoda M, Kimura K, Honma K, Hara H, Yoshida H, Yui K
  • Journal Title: Immunity Volume: 44 Issue: 3 Pages: 672-682
  • DOI: 10.1016/j.immuni.2016.02.011
  • Peer Reviewed
• [Journal Article] A Proteomic Approach Identifies Candidate Early Biomarkers to Predict Severe Dengue in Children (2016)
  • Author(s): Nhi DM, Huy NT, Ohyama K, Kimura D, Lan NT, Uchida L, Thuong NV, Nhon CT, Phuc le H, Mai NT, Mizukami S, Bao LQ, Doan NN, Binh NV, Quang LC, Karbwang J, Yui K, Morita K, Huong VT, Hirayama K.
  • Journal Title: PLoS Negl Trop Dis. Volume: 10 Issue: 2 Pages: e0004435-e0004435
  • DOI: 10.1371/journal.pntd.0004435
  • NAID: 120006666536
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] インターロイキン27を産生するCD4陽性T細胞によるマラリア原虫の感染に対する免疫防御の制御 (2016)
  • Author(s): 木村大輔・由井克之
  • Journal Title: First Author's Volume: - Pages: 021
  • DOI: 10.7875/first.author.2016.021
  • Open Access
• [Journal Article] Reduction of conventional dendritic cells during Plasmodium infection is dependent on activation induced cell death by type I and II interferons. (2015)
  • Author(s): Tamura T, Kimura K, Yui K, Yoshida S.
  • Journal Title: Exp Parasitol Volume: 159 Pages: 127-135
  • DOI: 10.1016/j.exppara.2015.09.010
  • Peer Reviewed
• [Journal Article] Haploinsufficiency of interferon regulatory factor 4 strongly protects against autoimmune diabetes in non-obese diabetic mice. (2015)
  • Author(s): Akazawa S, Kobayashi K, Kuriya G, Horie I, Yu L, Yamasaki H, Okita M, Nagayama Y, Matsuyama T, Akbari M, Yui K, Kawakami A, Abiru N.
  • Journal Title: Diabetologia Volume: 58 (11) Issue: 11 Pages: 2606-2614
  • DOI: 10.1007/s00125-015-3724-3
  • Peer Reviewed / Int'l Joint Research
• [Presentation] Interleukin-27 inhibits the generation of memory CD4+ T cells after treatment with anti-malaria drug (2017)
  • Author(s): D Kimura, M Miyakoda, M Akbari, K Kimura, H Hara, H Yoshida, K Yui
  • Organizer: The 13th Nagasaki-Singapore Medical Symposium
  • Int'l Joint Research / Invited
• [Presentation] T-cell responses to Plasmodium falciparum and Shistosoma mansoni infections in children living in the endemic region of Mbita, western Kenya (2017)
  • Author(s): C Kijyogi, D Kimura, B lamquoc, R Sonoda, K Yahata, O Kaneko, Y Ichinose, S Hamano, K. Yui
  • Organizer: The 13th Nagasaki-Singapore Medical Symposium
  • Int'l Joint Research
• [Presentation] マラリア原虫治癒後における免疫記憶消失はIL-27依存的である (2017)
  • Author(s): 木村大輔、都田真奈、M Akbari、木村一美、原博満、吉田裕樹、由井克之
  • Organizer: 第86回日本寄生虫学会大会
• [Presentation] T-cell responses to Plasmodium falciparum and Shistosoma mansoni infections in children living in the endemic region of Mbita, western Kenya (2017)
  • Author(s): C Kijyogi, D Kimura, LQ Bao, R Nakamura, K Yahata, O Kaneko, Y Ichinose, S Hamano, K Yui
  • Organizer: 第１６回あわじしま感染症・免疫フォーラム
• [Presentation] T-cell immune responses to Plasmodium falciparum and Schistosoma mansoni infection in asymptomatic children living in the endemic region of Mbita, western Kenya (2017)
  • Author(s): C Kijyogi, D Kimura, K Yui
  • Organizer: The 46th annual meeting of the Japanese Society for Immunology
• [Presentation] T-cell responses to Plasmodium falciparum and Schistosoma mansoni infections in asymptomatic children living in the endemic region of Mbyte, western Kenya (2017)
  • Author(s): C Kijyogi
  • Organizer: グルーバルヘルス合同大会2017
• [Presentation] マラリア原虫感染におけるIL-27依存的な免疫記憶抑制 (2016)
  • Author(s): 木村大輔、都田真奈、Akbari Masoud, 井手宏二、木村一美、原博満、吉田裕樹、由井克之
  • Organizer: 第85回日本寄生虫学会大会
  • Place of Presentation: 宮崎市民プラザ（宮崎県・宮崎市】
  • Year and Date: 2016-03-19
• [Presentation] CD4+ T cell responses of school children in Mbita Kenya, endemic region of Plasmodium falciparum and Schistosoma mansoni, (2016)
  • Author(s): Caroline Kijogi, Daisuke Kimura, Lam Quoc Bao, Risa Sonoda, Kazuhide Yahata, Osamu Kaneko, Shinjiro Hamano, Katsuyuki Yui,
  • Organizer: The 3rd International Symposium for the Promotion of Science and Technology Innovation
  • Place of Presentation: JICA研究所国際会議場（東京都・新宿区）
  • Int'l Joint Research
• [Presentation] IL-27-producing CD4+ T cells induced during malaria infection are distinct from Tr1 cells (2015)
  • Author(s): KIMURA Daisuke, MIYAKODA Mana, DOE Henrietta Terko, KIMURA Kazumi, HARA Hiromitsu, YOSHIDA Hiroki, YUI Katsuyuki
  • Organizer: 第44回日本免疫学会学術集会
  • Place of Presentation: 札幌コンベンションセンター（北海道・札幌市）
  • Year and Date: 2015-11-18
• [Presentation] Mechanisms underlying the induction of IL-27-producing CD4+ T cells during immune responses against intracellular pathogens (2015)
  • Author(s): DOE Henrietta Terko, KIMURA Kazumi, MIYAKODA Mana, masoud Akbari, Kazumi Kimura, YUI Katsuyuki,
  • Organizer: 64th annual meeting of American Society of Tropical Medicine and Hygine
  • Place of Presentation: Philadelphia, U.S.A.
  • Year and Date: 2015-10-25
  • Int'l Joint Research
• [Presentation] Regulation of immune responses by IL-27-producing CD4+ T cells during malaria infection (2015)
  • Author(s): K. Yui
  • Organizer: The 12th NUS-Nagasaki joint symposium
  • Place of Presentation: NUS, Singapore
  • Year and Date: 2015-06-11
  • Int'l Joint Research / Invited
• [Presentation] IL-27-producing CD4+ T cells regulate protective immune responses during malaria infection (2015)
  • Author(s): KIMURA Daisuke, MIYAKODA Mana, DOE Henrietta Terko, KIMURA Kazumi, Hiromitsu Hara, Hiroki Yoshida, YUI Katsuyuki
  • Organizer: 25th Annual molecular parasitology vector biology Symposium
  • Place of Presentation: Athens, GO USA
  • Year and Date: 2015-04-28
  • Int'l Joint Research / Invited
• [Remarks] 長崎大学大学院医歯薬学総合研究科新興感染症病態制御学系専攻免疫学分野
  • URL: http://www.med.nagasaki-u.ac.jp/mmi/im/