4D imaging of brain and the immune system during cerebral malaria

• Project/Area Number: 25293100
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Parasitology (including sanitary zoology)
• Research Institution: Osaka University
• Principal Investigator: Coban Cevayir 大阪大学, 免疫学フロンティア研究センター, 教授 (00397712)
• Research Collaborator: 川合 覚 獨協医科大学, 医学部, 准教授 ; 吉岡 芳親 大阪大学, 免疫学フロンティア研究センター生体機能イメージング, 教授 ; 審良 静男 大阪大学, 免疫学フロンティア研究センター, 教授 ; 堀井 俊宏 大阪大学微生物病研究所, 分子原虫学分野, 教授 ; 石井 健 大阪大学, 免疫学フロンティア研究センターワクチン学, 教授
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000); Fiscal Year 2015: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2014: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2013: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
• Keywords: 感染症 / 免疫学 / マラリア / Olfactory Bulb / Plasmodium bergheiANKA / Immunology / Cerebral Malaria / Imaging / MRI / Multiphoton imaging / Olfactory bulb / smell loss / Cerebral malaria / imaging / two-photon microscopy / olfactory bulb / cerebral malaria / multi-photon microscopy

Outline of Final Research Achievements

The dysfunction of BBB is the main feature of cerebral malaria; however, little is known how it occurs. We have shown by ultra-high field MRI and multiphoton microscopy that the olfactory bulb is physically and functionally damaged by Plasmodium parasites. The trabecular small capillaries comprising the olfactory bulb show parasite accumulation and cell occlusion followed by microbleeding, events associated with high fever and cytokine storm. Early detection of olfaction loss and blockade of pathological cell recruitment may offer potential therapeutic strategies.

Research Products

• [Journal Article] Hydroxypropyl-β-Cyclodextrin Spikes Local Inflammation That Induces Th2 Cell and T Follicular Helper Cell Responses to the Coadministered Antigen. (2015)
  • Author(s): Onishi M, Ozasa K, Kobiyama K, Ohata K, Kitano M, Taniguchi K, Homma T, Kobayashi M, Sato A, Katakai Y, Yasutomi Y, Wijaya E, Igarashi Y, Nakatsu N, Ise W, Inoue T, Yamada H, Vandenbon A, Standley DM, Kurosaki T, Coban C, Aoshi T, Kuroda E, Ishii KJ.
  • Journal Title: The Journal of Immunology Volume: 194 Issue: 6 Pages: 2673-2682
  • DOI: 10.4049/jimmunol.1402027
  • Peer Reviewed / Open Access
• [Journal Article] Label-free Raman imaging of the macrophage response to the malaria pigment hemozoin (2015)
  • Author(s): Hobro AJ, Pavillon N, Fujita K, Ozkan M, Coban C, Smith NI
  • Journal Title: Analyst Volume: 140 Issue: 7 Pages: 2350-2359
  • DOI: 10.1039/c4an01850h
  • Peer Reviewed / Open Access
• [Journal Article] Hemozoin as a novel adjuvant for inactivated whole virion influenza vaccine. (2014)
  • Author(s): Uraki R, Das SC, Hatta M, Kiso M, Iwatsuki-Horimoto K, Ozawa M, Coban C, Ishii KJ, Kawaoka Y.
  • Journal Title: Vaccine Volume: 32(41) Issue: 41 Pages: 5295-5300
  • DOI: 10.1016/j.vaccine.2014.07.079
  • Peer Reviewed / Open Access
• [Journal Article] Olfactory plays a key role in spatiotemporal pathogenesis of cerebral malaria. (2014)
  • Author(s): H. Zhao, T. Aoshi, S. Kawai, Y. Mori, A. Konishi, M. Ozkan, Y. Fujita, Y. Haseda, M. Shimizu, M. Kohyama, K. Kobiyama, K. Eto, J. Nabekura, T. Horii, T. Ishino, M. Yuda, H. Hemmi, T. Kaisho, S. Akira, M. Kinoshita, K. Tohyama, Y. Yoshioka, K. J. Ishii, C. Coban
  • Journal Title: Cell Host Microbe Volume: 15 Issue: 5 Pages: 551-563
  • DOI: 10.1016/j.chom.2014.04.008
  • Peer Reviewed / Open Access
• [Journal Article] Olfactory is an overlooked site for the initiation of cerebral malaria (2014)
  • Author(s): Zhao H, Aoshi T, Kawai S, Mori Y, Konishi A, Ozkan M, Fujita Y, Haseda Y, Shimizu M, Kohyama M, Kobiyama K, Eto K, Nabekura J, Horii T, Ishino T, Yuda M, Hemmi H, Kaisho T, Akira S, Kinoshita M, Tohyama K, Yoshioka Y, Ishii KJ, Coban C
  • Journal Title: Cell Host Microbe Volume: in press
  • Peer Reviewed
• [Journal Article] Hemozoin is a potent adjuvant for hemagglutinin split vaccine without pyrogenicity in ferrets (2014)
  • Author(s): Onishi M, Kitano M, Taniguchi K, Homma T, Kobayashi M, Sato A, Coban C, Ishii KJ
  • Journal Title: Vaccine Volume: in press
  • Peer Reviewed
• [Journal Article] Nonagonistic Dectin-1 ligand transforms CpG into a multitask nanoparticulate TLR9 agonist. (2014)
  • Author(s): Kobiyama K, Aoshi T, Narita H, Kuroda E, Hayashi M, Tetsutani K, Koyama S, Mochizuki S, Sakurai K, Katakai Y, Yasutomi Y, Saijo S, Iwakura Y, Akira S, Coban C, Ishii KJ.
  • Journal Title: Proc Natl Acad Sci U S A. Volume: 111 Issue: 8 Pages: 3086-3091
  • DOI: 10.1073/pnas.1319268111
  • Peer Reviewed
• [Journal Article] DNA vaccines: A simple DNA sensing matter? (2013)
  • Author(s): Coban C, Kobiyama K, Jounai N, Tozuka M, Ishii KJ
  • Journal Title: Human Vaccines and Immunotherapeutics Volume: 9 (10) Pages: 23912600-23912600
  • Peer Reviewed
• [Journal Article] Raman spectroscopic analysis of malaria disease progression via blood and plasma samples. (2013)
  • Author(s): Hobro AJ, Konishi A, Coban C, Smith NI.
  • Journal Title: Analyst Volume: 138(14) Issue: 14 Pages: 3927-3933
  • DOI: 10.1039/c3an00255a
  • Peer Reviewed
• [Presentation] Immunopathology of malaria: search for new drug targets (2016)
  • Author(s): C Coban
  • Organizer: The 89th Annual Meeting of the Japanese Pharmacological Society
  • Place of Presentation: Pacifico Yokohama, Yokohama, JAPAN.
  • Year and Date: 2016-03-09
  • Int'l Joint Research / Invited
• [Presentation] Tissue-specific Immunopathology during Malaria (2016)
  • Author(s): C Coban
  • Organizer: The 5th NIF Winter School on Advanced Immunology
  • Place of Presentation: Awaji Island, Hyogo, JAPAN
  • Year and Date: 2016-01-17
  • Int'l Joint Research / Invited
• [Presentation] Tissue-specific Immunopathology during Malaria (2015)
  • Author(s): C Coban
  • Organizer: Global Network Forum on Infection and Immunity 2015
  • Place of Presentation: Chiba University, Chiba, JAPAN.
  • Year and Date: 2015-11-14
  • Int'l Joint Research / Invited
• [Presentation] Imaging malaria immunopathology (2015)
  • Author(s): C Coban
  • Organizer: Department of Pediatrics, Saint Louis University School of Medicine
  • Place of Presentation: St. Louis, MO, USA.
  • Year and Date: 2015-08-07
  • Int'l Joint Research / Invited
• [Presentation] Tissue-specific Immunopathology during Malaria (2015)
  • Author(s): C Coban
  • Organizer: The 6th Congress of the FIMSA (Federation of Immunological Societies of Asia Oceania)
  • Place of Presentation: Marina Bay Sands Convention Center, SINGAPORE
  • Year and Date: 2015-06-30
  • Int'l Joint Research / Invited
• [Presentation] Tissue-specific Immunopathology during Malaria (2015)
  • Author(s): C Coban
  • Organizer: RIKEN IMS-JSI International Symposium on Immunology 2015, Infection and Immunit
  • Place of Presentation: Pacifico Yokohama, Yokohama, JAPAN.
  • Year and Date: 2015-06-18
  • Int'l Joint Research / Invited
• [Presentation] Imaging malaria immunopathology (2014)
  • Author(s): C. Coban
  • Organizer: The 13th Awaji International Forum on Infection and Immunity in Nara
  • Place of Presentation: Nara
  • Year and Date: 2014-09-23 – 2014-09-26
  • Invited
• [Presentation] Host-Pathogen Interactions during Malaria Infection. (2014)
  • Author(s): C. Coban
  • Organizer: The University of Tokyo, Major in Animal Life Sciences, Dept. of Animal Resource Sciences,
  • Place of Presentation: Tokyo
  • Year and Date: 2014-07-10
  • Invited
• [Presentation] Host-Pathogen Interactions in the Context of Malaria (2014)
  • Author(s): C. Coban
  • Organizer: The 2nd International Molecular Immunology & Immunogenetics Congress (MIMIC-II 2014).
  • Place of Presentation: Antalya, Turkey
  • Year and Date: 2014-04-27 – 2014-04-30
  • Invited
• [Presentation] A new gateway for cerebral malaria immunopathology. (2013)
  • Author(s): Coban C
  • Organizer: International Symposium TCUID 2013 organized by FIRST Program: AKIRA Project.
  • Place of Presentation: Icho Kaikan, Osaka University, Osaka, JAPAN
  • Invited
• [Presentation] Immune responses to malaria parasites (2013)
  • Author(s): Coban C
  • Organizer: 22nd Turkish Immunology Conference
  • Place of Presentation: Cesme, TURKEY
  • Invited
• [Presentation] Imaging cerebral malaria immunpathology (2013)
  • Author(s): Coban C
  • Organizer: The 42th Annual Meeting of Japanese Society for Immunology,
  • Place of Presentation: Chiba, JAPAN
• [Presentation] A new gateway for cerebral malaria immunopathology (2013)
  • Author(s): Coban C
  • Organizer: The 5th International Conference on Crossroads between Innate and Adaptive Immunity
  • Place of Presentation: Corfu Island, GREECE
• [Presentation] Imaging cerebral malaria pathology (2013)
  • Author(s): Coban C
  • Organizer: The 12th Awaji International Forum on Infection and Immunity
  • Place of Presentation: Hyogo, JAPAN
• [Presentation] Imaging cerebral malaria
  • Author(s): Coban C
  • Organizer: Minisymposium on malaria immunopathology.
  • Place of Presentation: IFReC, Osaka University, Osaka, JAPAN.
  • Invited
• [Book] Biological DNA Sensor: The Impact of Nucleic Acids on Diseases and Vaccinology (2013)
  • Author(s): Tang CK, Coban C, Akira S, Ishii KJ.
  • Publisher: Elsevier
• [Book] Biological DNA Sensor: The Impact of Nucleic Acids on Diseases and Vaccinology (2013)
  • Author(s): 2- Coban C, Tozuka M, Jounai N, Kobiyama K, Takeshita F, Tang CK, Ishii KJ.
  • Publisher: Elsevier
• [Remarks] Olfactory plays a key role in pathogenesis...
  • URL: http://www.ifrec.osaka-u.ac.jp/en/research/20140515-0701.htm
• [Remarks] 脳マラリアの新たな診断と治療のターゲットを発見
  • URL: http://resou.osaka-u.ac.jp/ja/research/2014/20140515_1
• [Remarks] http://malimm.ifrec.osaka-u.ac.jp/
• [Patent(Industrial Property Rights)] Diagnosis and medical treatment for cerebral malaria (2014)
  • Inventor(s): Coban et al
  • Industrial Property Rights Holder: Coban et al
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-03-27
• [Patent(Industrial Property Rights)] Synthetic hemozoin as a contrast reagent for MRI. (2013)
  • Inventor(s): Yoshioka and Coban et al
  • Industrial Property Rights Holder: Yoshioka and Coban et al
  • Industrial Property Rights Type: 特許
  • Filing Date: 2013-08-23