Glucose metabolism and Molecular basis analysis for immunoprotective mechanisms angainst Babesia spp. Infection

• Project/Area Number: 12556055
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 展開研究
• Research Field: Applied veterinary science
• Research Institution: THE UNIVERSITY OF TOKYO
• Principal Investigator: ONO Kenichiro THE UNIVERSITY OF TOKYO, Graduate School of Agriculturral and Life Sciences, The University of Tokyo, Professor (50111480)
• Co-Investigator(Kenkyū-buntansha): KARAKI Hideaki THE UNIVERSITY OF TOKYO, Graduate School of Agricultural and Life Sciences, Associate Professor (60011912) ; MATSUMOTO Yoshitugu THE UNIVERSITY OF TOKYO, Graduate School of Agricultural and Life Sciences, Associate Professor (00173922) ; INABA Mutsumi THE UNIVERSITY OF TOKYO, Graduate School of Agricultural and Life Sciences, Associate Professor (00183179) ; MATSUKI Naoaki THE UNIVERSITY OF TOKYO, Graduate School of Agricultural and Life Sciences, Associate Professor (40251417) ; YASUDA Mitsuya Medicinal Safety Research Laboratory Sankyo Co.Ltd., Chief Researcher
• Project Period (FY): 2000 – 2001
• Project Status: Completed (Fiscal Year 2001)
• Budget Amount: ¥13,000,000 (Direct Cost: ¥13,000,000); Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000); Fiscal Year 2000: ¥10,500,000 (Direct Cost: ¥10,500,000)
• Keywords: Babesia spp / glucose metabolism / membrane specific protein / protective immunity / IL-12 / IL-12 p70 / stimulating factor for IL-12 production / IRBM / Il-12産生刺激物質

Research Abstract

1) Glucose metabolism : Using short term cultivation system established, glucose uptake system was investigated in Babesia microti and B. rodhaini infected erythrocytes. Based on the labeled D-glucose uptake, both infected erythrocytes showed new glucose transport system, which revealed different character between two Babesia protozoa. On the morphological examination, specific changes observed in both infected erythrocytes.
2) Development of anti-protozoan drugs : Based on the results of glucose metabolism related enzyme activities, some candidate designs of anti-protozoan drugs was imaged. However, no drug was developed.
3) Molecular analysis for protozoan membrane proteins : Based on the results of molecular analysis for surface membrane proteins of infected erythrocytes, one protein enhanced IL-12 production from splenic macrophage was detected. However, full sequence of its was not established.
4) Immunological protective mechanism for protozoa : Differentiation for Th1 cells was an important factor for prevention of protozoan infection. Two phase secretion of IL-12 p70 was closely related to this differentiation. However, other mechanism beside IL-12 p70 was necessary for the elimination of protozoa.
5) Development of the biological response modifier : The heat stable protein in culture supernatant of infected erythrocytes was detected. Since this protein remarkably enhanced IL-12 production from splenic macrophage, iit was considered that one of the candidate for biological response modifier.

Research Products

• [Journal Article] Spleen and serum IL-12 p70 concentrations in BALB/c mice infected with Babesia microti and Babesia rodhaini. (2004)
  • Author(s): Ohmori, T., Fukuda, T., Matsuki, N., Ono, K.
  • Journal Title: J.Vet.Med.Sci. (Submitted)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Splenic IL-12 concentration, delayed type hypersensitivity, IL-4 and IFN-gamma mRNA expression of CD4 positive T cells in C57BL/6, CBA/1, and BALB/c mice infected with Babesia microti and Babesia rodhaini. (2004)
  • Author(s): Ohmori, T., Fukuda, T., Matsuki, N., Ono, K.
  • Journal Title: J.Vet.Med.Sci. (Submitted)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Glucose uptake activity in murine red blood cells infected with Babesia microti and Babesia rodhaini infected erythrocytes. (2003)
  • Author(s): Ohmori, T., Adachi, K., Fukuda, Y., Matsuki, N., Ono, K.
  • Journal Title: J.Vet.Med.Sci. (Submitted)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Effects of macrophage derived IL-12 on splenic Th1 and Th2 subsets differentiation in early phase of infection with Babesia microti and Babesia rodhaini infection in mice. (2003)
  • Author(s): Hashiguchi-Katoh, R., Shikano, S., Shimada, T., Ono, K.
  • Journal Title: J.Vet.Med.Sci. (Submitted)
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] The number of MHC class II positive splenic antigen presenting cell in Babesia microti and Babesia rodhaini nfected mice. (1999)
  • Author(s): HASHIGUCHI R., et al.
  • Journal Title: J.Protozool.Res. 9 Pages: 41-48
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] The number of MHC class II positive splenic antigen presenting cell in Babesia microti and Babesia rodhaini nfected mice. (1999)
  • Author(s): Hashiguchi-Katoh, R., Shikano, S., Shimada, T., Ono, K.
  • Journal Title: J.Protozool. Res. 9 Pages: 41-98
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Mitochondrial function of Babesia microti and Babesia rodhini. (1998)
  • Author(s): SHIKANO S., et al.
  • Journal Title: Int.J.Parasitol. 28 Pages: 567-570
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Mitochondrial function in Babesia microti and Babesia rodhaini. (1998)
  • Author(s): Shikano, S., Katoh, R., Adachi, K., Bonkobara, M., Inaba, M., Ono, K.
  • Journal Title: Int.J.Parasitology 28 Pages: 567-570
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Glucose uptake activity in murine red blood cells infected with Babesia microti and Babesia rodhaini infected ervthrocytes.
  • Author(s): OHMORI R., et al.
  • Journal Title: J.Vet.Med.Sci. (発表予定)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Effects of macrophage derived IL-12 on splenic Th1 and Th2 subsets differentiation in early phase of infection with Babesia microti and Babesia rodhaini infection in mice.
  • Author(s): HASHIGUCHI R., et al.
  • Journal Title: J.Vet.Med.Sci. (発表予定)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Spleen and serum IL-12 p70 concentrations in BALB/c mice infected with Babesia microti and Babesia rodhaini.
  • Author(s): OHMORI R., et al.
  • Journal Title: J.Vet.Med.Sci. (発表予定)
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Splenic IL-12 concentration, delayed type hypersensitivity, IL-4 and IFN-gamma mRNA expression of CD4 positive T cells in C57BL/6, CBA/1, and BALB/c mice infected with Babesia microti and Babesia rodhaini.
  • Author(s): OHMORI R., et al.
  • Journal Title: J.Vet.Med.Sci. (発表予定)
  • Description: 「研究成果報告書概要(和文)」より
• [Publications] SHIKANO S. et al.: "Mitochondrial function of Babesia microti and Babesia rodhini"Int.J.Parasitol. 28. 567-570 (1998)
• [Publications] HASHIGUCHI R. et al.: "The number of MHC class II positive splenic antigen presenting cell in Babesia microti and Babesia rodhaini nfected mice"J.Protozool.Res.. 9. 41-48 (1999)
• [Publications] ONO K. et al.: "Splenic Th1 and Th2 subsets differentiation in early phase of infection with Babesia microti and Babesia rodhaini infection in mice"J.Vet Med.Sci.. (発表予定).
• [Publications] OHMORI T. et al.: "Glucose transport activity in murine red blood cells infected with Babesia rodhaini and Babesia microti"J.Vet.Med.Sci.. (発表予定).
• [Publications] ONO K. et al.: "Effects of macrophage derived IL-12 on splenic Th1 and Th2 subsets differentiation in early phase of infection with Babesia microti and Babesia rodhaini infection in mice"J.Vet.Med.Sci.. (発表予定).
• [Publications] ONO K. et al.: "Mitochondrial function of Babesia microti and Babesia rodhini."J Vet.Med.Sci.. (発表予定).
• [Publications] ONO K. et al.: "The number of MHC class II positive splenic antigen presenting cell in Babesia microti and Babesia rodhaini nfected mice."J.Vet.Med.Sci.. (発表予定).
• [Publications] ONO K. et al.: "Splenic Th1 and Th2 subsets differentiation in early phase of infection with Babesia microti and Babesia rodhaini infection in mice."J.Vet Med.Sci.. (発表予定).