Host-parasite interaction in eythroblastic infection during malaria

• Project/Area Number: 15K08441
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: National Institute of Infectious Diseases (2017-2018); Gunma University (2015-2016)
• Principal Investigator: Hisaeda Hajime 国立感染症研究所, 寄生動物部, 部長 (50243689)
• Research Collaborator: Imai Takashi
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: マラリア / CD8 T細胞 / 赤芽球 / 宿主病原体相互作用 / プロテアソーム / CD8T細胞 / ワクチンモデル開発 / ウガンダ / フォスファチジルセリン / マクロファージ / CD8Ｔ細胞 / 赤芽級

Outline of Final Research Achievements

The proposed aims, 1) recognition of infected erythroblasts by CD8 T cells, 2) growth of malaria parasites in erythroblasts, and 3) protective mechanisms of CD8 T cells against infected erythroblasts, have been achieved. We clarified that CD8 T cells recognize infected erythroblasts and exert cytotoxicity mediated by FasL to translocation of phosphatidylserine to surface of infected erythroblasts, resulting in higher susceptibility to phagocytosis by macrophages. Thus, CD8 T cells play protective roles in blood-stage malaria by enhancing clearance of infected erythrocytes in collaboration with macrophages.

Academic Significance and Societal Importance of the Research Achievements

これまでよく分からなかったCD8Ｔ細胞の赤血球ステージのマラリアに対する防御機構の詳細を明らかにすることで、新たなワクチン戦略を提唱できる。これまでは抗体を誘導することを目的とし、細胞表面の分子を標的としたが、免疫による選択圧で多型を示すものが多く、ワクチン効果は限定的であった。一方、CD8Ｔ細胞は細胞内部の多型性の少ない抗原も認識できるので、抗原の多様性に制限を受けない幅広い効果を発揮するワクチンとなることが期待できる。

Research Products

• [Int'l Joint Research] グル大学/ラチョー病院(ウガンダ)
• [Int'l Joint Research] グル大学/ラチョー病院(ウガンダ)
• [Journal Article] Suppression of obesity by an intestinal helminth through interactions with intestinal microbiota. (2019)
  • Author(s): Shimokawa C, Obi S, Shibata M, Olia A, Imai T, Suzue K, Hisaeda H.
  • Journal Title: Infection and Immunity Volume: 印刷中 Issue: 6
  • DOI: 10.1128/iai.00042-19
  • Peer Reviewed / Open Access
• [Journal Article] Escherichia coli mediated resistance of Entamoeba histolytica to oxidative stress is triggered by oxaloacetate. (2018)
  • Author(s): Shaulov Y, Shimokawa C, Trebicz-Geffen M, Nagaraja S, Methling K, Lalk M, Weiss-Cerem L, Lamm AT, Hisaeda H, Ankri S.
  • Journal Title: PLoS Pathongen Volume: 14 Issue: 10 Pages: e1007295-e1007295
  • DOI: 10.1371/journal.ppat.1007295
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Intestinal Inflammation-Mediated Clearance of Amebic Parasites Is Dependent on IFN-γ (2018)
  • Author(s): Shimokawa C, Senba M, Kobayashi S, Kikuchi M, Obi S, Olia A, Hamano S, Hisaeda H
  • Journal Title: Journal of Immunology Volume: 200 Issue: 3 Pages: 1101-1109
  • DOI: 10.4049/jimmunol.1700806
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Mast Cells Are Crucial for Induction of Group 2 Innate Lymphoid Cells and Clearance of Helminth Infections. (2017)
  • Author(s): Shimokawa C, Kanaya T, Hachisuka M, Ishiwata K, Hisaeda H, Kurashima Y, Kiyono H, Yoshimoto T, Kaisho T, Ohno H.
  • Journal Title: Immunity Volume: 46 Issue: 5 Pages: 863-874
  • DOI: 10.1016/j.immuni.2017.04.017
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] A possible origin population of pathogenic intestinal nematodes, Strongyloides stercoralis, unveiled by molecular phylogeny (2017)
  • Author(s): Nagayasu E, Aung MPPTHH, Hortiwakul T, Hino A, Tanaka T, Higashiarakawa M, Olia A, Taniguchi T, Win SMT, Ohashi I, Odongo-Aginya EI, Aye KM, Mon M, Win KK, Ota K, Torisu Y, Panthuwong S, Kimura E, Palacpac NMQ, Kikuchi T, Hirata T, Torisu S, Hisaeda H, Horii T, Fujita J, Htike WW, Maruyama H
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 4844-4844
  • DOI: 10.1038/s41598-017-05049-x
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Plasmodium berghei ANKA causes intestinal malaria associated with dysbiosis (2015)
  • Author(s): Taniguchi T, Miyauchi E, Nakamura S, Hirai M, Suzue K, Imai T, Nomura T, Handa T, Okada H, Shimokawa C, Onishi R, Olia A, Hirata J, Tomita H, Ohno H, Horii T, Hisaeda H
  • Journal Title: Scientific Reports Volume: 5:15699 Issue: 1 Pages: 1-12
  • DOI: 10.1038/srep15699
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] A transient resistance to blood-stage malaria in interferon-γ-deficient mice through impaired production of host cells preferred by malaria parasites (2015)
  • Author(s): Okada H, Suzue K, Imai T, Taniguchi T, Shimokawa C, Onishi R, Hirata J, and Hisaeda H
  • Journal Title: Frontiers in Microbiology Volume: 6:600 Pages: 1-8
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Book] 人獣共通感染症 (2016)
  • Author(s): 久枝一
  • Total Pages: 6
  • Publisher: 医薬ジャーナル社
• [Patent(Industrial Property Rights)] 制御性T細胞増強剤並びにそれを含む医薬及び食品組成物 (2017)
  • Inventor(s): 久枝一、下川周子、和泉孝志、大嶋紀安、大野博司、加藤完
  • Industrial Property Rights Holder: 久枝一、下川周子、和泉孝志、大嶋紀安、大野博司、加藤完
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2017-094949
  • Filing Date: 2017