Elucidation of mechanisms by which host immune cells kill protozoan parasites and development of antiparasitic peptides

• Project/Area Number: 15K20840
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Integrative animal science; Veterinary medical science
• Research Institution: Hokkaido University
• Principal Investigator: Terkawi Alaa 北海道大学, 医学研究科, 助教 (00723074)
• Research Collaborator: Kato Kentaro 原虫病研究センター帯広畜産大学 ; Takano Ryo 原虫病研究センター帯広畜産大学
• Project Period (FY): 2015-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: Macrophages / Neutrophils / Phagocytes / Effector molecules / neutrophils / effector molecules / DNA Microarray / DEFB130 / CTSL

Outline of Final Research Achievements

Understanding the molecular defense mechanism of phagocytes and identifying their effector molecules against malarial parasites may provide important clues for the discovery of new therapies. Macrophages and neutrophils are professional phagocytes that play key role in the innate immune response against infection through their ability to rapidly recognize and kill microorganisms. An attempt was made to identify the host effector molecules derived from macrophages and neutrophils that kill malaria parasites using DNA microarray technology.
Results suggested that DEFB130 from macrophages and CTSL from neutrophils are involved in the clearance mechanism of malarial parasites. The data obtained from this project broaden our knowledge on the immunological response of macrophages and neutrophils to malaria parasites and shed light on a new target for therapeutic intervention.

Research Products

• [Journal Article] Involvement of β-defensin 130 (DEFB130) in the macrophage microbicidal mechanisms for killing Plasmodium falciparum (2017)
  • Author(s): Terkawi MA, Takano R, Furukawa A, Murakoshi F, Kato K.
  • Journal Title: Sci Rep Volume: 7 Issue: 1 Pages: 41772-41772
  • DOI: 10.1038/srep41772
  • NAID: 120006219999
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Isolation and co-cultivation of human macrophages and neutrophils with Plasmodium falciparum-parasitized erythrocytes: An optimized system to study the phagocytic activity to malarial parasites (2016)
  • Author(s): Terkawi MA, Takano, R, Kato K.
  • Journal Title: Parasitology International Volume: In press Issue: 5 Pages: 30025-3
  • DOI: 10.1016/j.parint.2016.03.005
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Dextran sulfate inhibits acute Toxoplama gondii infection in pigs (2016)
  • Author(s): Kato K, Murata Y, Horiuchi N, Inomata A, Terkawi MA, Ishiwa A, Ogawa Y, Fukumoto S, Matsuhisa F, Koyama K.
  • Journal Title: Parasites & Vectors Volume: 9 Issue: 1 Pages: 134-134
  • DOI: 10.1186/s13071-016-1421-9
  • NAID: 120006390935
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Depletion of phagocytic cells during nonlethal Plasmodium yoelii infection causes severe malaria characterized by acute renal failure in Mice (2016)
  • Author(s): Terkawi MA, Nishimura M, Furuoka H, Nishikawa Y.
  • Journal Title: Infection & Immunty Volume: 84 Issue: 3 Pages: 845-855
  • DOI: 10.1128/iai.01005-15
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Characterization of Toxoplasma gondii glyoxalase 1 and evaluation of inhibitory effects of curcumin on the enzyme and parasite cultures. (2015)
  • Author(s): Youn-Kyoung Goo, Junya Yamagishi, Akio Ueno, Mohamad Alaa Terkawi, Gabriel Oluga Aboge, Dongmi Kwak, Yeonchul Hong, Dong-Il Chung, Makoto Igarashi, Yoshifumi Nishikawa and Xuenan Xuan.
  • Journal Title: Parasites & Vectors Volume: 8：654 Issue: 1 Pages: 1-8
  • DOI: 10.1186/s13071-015-1268-5
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Molecular detection and characterization of Babesia bovis, Babesia bigemina, Theileria species and Anaplasma marginale isolated from cattle in Kenya. (2015)
  • Author(s): Adjou Moumouni PF, Aboge GO, Terkawi MA, Masatani T, Cao S, Kamyingkird K, Jirapattharasate C, Zhou M, Wang G, Liu M, Iguchi A, Vudriko P, Ybanez AP, Inokuma H, Shirafuji-Umemiya R, Suzuki H, Xuan X.
  • Journal Title: Parasites & Vectors Volume: 8 Issue: 1 Pages: 496-496
  • DOI: 10.1186/s13071-015-1106-9
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Optimization of a Fluorescence-Based Assay for Large-Scale Drug Screening against Babesia and Theileria Parasites. (2015)
  • Author(s): Rizk, M.A., El-Sayed, S.A., Terkawi, M.A., Youssef, M.A., El Said el Sel, S., Elsayed, G., El-Khodery, S., El-Ashker, M., Elsify, A., Omar, M., Salama, A., Yokoyama, N., and Igarashi, I.
  • Journal Title: PLoS One. Volume: 10 Issue: 4 Pages: e0125276-e0125276
  • DOI: 10.1371/journal.pone.0125276
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Involvement of β-defensin 130 (DEFB130) in the macrophage microbicidal mechanisms for killing Plasmodium falciparum (2017)
  • Author(s): Terkawi MA, Takano T, Kato K.
  • Organizer: Japan-Brazil Malaria Research Workshop
  • Place of Presentation: Brazil, Sao Paulo
  • Year and Date: 2017-03-15
  • Int'l Joint Research
• [Presentation] Differentiated gene profile of neutrophils induced by phagocytosis of Plasmodium falciparum-parasitized erythrocytes. (2016)
  • Author(s): Terkawi MA
  • Organizer: The 85th Annual Meeting of the Japanese Society of Parasitology.
  • Place of Presentation: 宮崎市民プラザ（宮崎市）
  • Year and Date: 2016-03-19
• [Presentation] Involvement of a novel cysteine-rich cationic low molecular weight protein in the macrophage microbicidal mechanisms for killing Plasmodium falciparum (2015)
  • Author(s): Terkawi MA
  • Organizer: The 14th Awaji international forum on infection and immunity
  • Place of Presentation: 淡路夢舞台国際会議場（淡路市）
  • Year and Date: 2015-09-08