2005 Fiscal Year Final Research Report Summary
Immunoregulatory role of MΦ/DCs in the liver of murine malaria infected mice
| Project/Area Number |
16590343
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Parasitology (including Sanitary zoology)
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| Research Institution | University of the Ryukyus |
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Principal Investigator |
WATANABE Hisami University of the Ryukyus, Center of Molecular Biosciences, Professor, 遺伝子実験センター, 教授 (50143756)
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| Co-Investigator(Kenkyū-buntansha) |
MK Mannoor Division of Tropical Parasitology, Faculty of Medicine, Assistant Professor, 医学部, 助手 (70347136)
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| Project Period (FY) |
2004 – 2005
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| Keywords | Murine malaria / NKT cells / Dendritic cells (DC) / Myeloid DC / Plasmacytoid DC / Cytokine / Apoptosis inhibitor / Disease syndromes |
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| Research Abstract |
We have already reported that one subset of NKT cells, known as CD3^<int>IL-2Rβ+NK1.1-subset, expanded in the liver of P.yoelli 17XNL-infected C57BL/6(B6) mice and contributed to protection against malaria. On the other hand, accumulating results of our studies suggested that liver dendritic cells (DCs) might play a critical role in the regulation of immune responses through activation of liver NKT cells after malarial infection. However, this approach has not been clearly elucidated. In this study we attempted to analyze the phenotype and function of liver DCs in malaria infected mice.
DCs are classified into two majour subpopulations ; myeloid DC (mDC) and plasmacytoid DC (pDC). Murine liver had high absolute number of PDCA-1+CD11c^<low>I-A-B220+DC (pDC) which produced IFN-α by stimulation with CpG in vitro. PDCA-1-CD11c^<high>I-A+B220-DC (mDC) were dominant in the spleen. DCs of both phenotypes were able to produce IL-12, IL-10 and TNFα. CD11c^<low>I-A-DC isolated from malaria infect
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ed mice increased in the liver and spleen at acute phase (7 days). These cells showed high expression of CD86 but decreased PDCA-1 expression and IFN-α production. I-A-CD11c^<low>DCs isolated from infected mice showed impaired production of cytokines as compared with mDCs. PDCA-1^+ cells in CD11c^<low>I-A- fraction of liver and spleen reappeared at recovery phase (after 25 days) of malarial infection. These results indicate that while mDCs activate NKT cells via cytokines and that activated NKT cells promote the protective activity and disease syndromes in malaria infected mice. pDCs induce the immunosuppressive effects due to impaired production of IFN-α. AIM (apoptosis inhibitor expressed by MΦ) deficient mice lack some of MΦ and DC functions and were found to recover more quickly from malarial infection than B6 mice. γδT cells expanded in the liver and spleen, especially in the recovery phase. These findings clearly showed the phenotypical and functional change of DCs in the liver and may support the view that liver DC regulate the function of NKT cells in the liver after malarial infection. Less
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Research Products
(13 results)
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[Journal Article] Reasons why DBA/2 mice are resistant to malarial infection : expansion of CD3^int B220^+ gammadelta T cells with double-negative CD4^- CD8^- phenotype in the liver.2006
Author(s)
Bakir, H.Y., Tomiyama-Miyaji, C., Watanabe, H., Nagura, T., Kawamura, T., Sekikawa H, Abo, T.
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Journal Title
Immunology 117
Pages: 127-135
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Reasons why DBA/2 mice are resistant to malarial infection : expansion of CD3^<int> B220^+ gammadelta T cells with double-negative CD4^- CD8^- phenotype in the liver.2006
Author(s)
Bakir, H.Y., Tomiyama-Miyaji, C., Watanebe, H., Nagura, T., Kawamura, T., Sekikawa H, Abo, T.
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Journal Title
Immunology 117
Pages: 127-135
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Protection against malaria by anti-erythropoietin antibody due to suppression of erythropoiesis in the liver and at other sites.2005
Author(s)
Tsubata, S., Ebe, K., Kawamura, T., Ishimoto, Y., Tomiyama-Miyaji, C., Watanabe, H., Sekikawa, H., Aoyagi, Y., Abo, T.
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Journal Title
Immunology and Cell Biology 83
Pages: 638-642
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Protection against malaria by anti-erythropoietin antibody due to suppression of erythropoiesis in the liver and at other sites.2005
Author(s)
Tsubata, S., Ebe, K., Kawamura, T., Ishimoto, Y., Tomiyama-Miyaji, C., Watanabe.H., Sekikawa, H., Aoyagi, Y., Abo, T.
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Journal Title
Immuno Cell Biol 83
Pages: 638-642
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Pyrimethamine-Sulfadoxine treatment of uncomplicated Plasmodium falciparum malaria in Lao PDR.2005
Author(s)
Mannoor, M.K., Vanisaveth, V., Keokhamphavanh, B., Toma, H., Watanabe, H., Kobayashi, J., Hatabu, T., Taguchi, N., Hongvangthong, B., Phetsouvanh, R., Phompida, S., Kano, S., Sato, Y.
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Journal Title
Southeast Asian J.Trop.Med.Public Health 36
Pages: 1092-1095
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Increase in hepatic NKT cells in leukocyte cell-derived chemotaxin 2-deficient mice contributes to severe Concanavalin A-induced hepatitis.2004
Author(s)
Saito, T., Okumura, A., Watanabe, H., Asano, M., Ishida-Okawara, A., Sakagami, J., Sudo, K., Hatano-Yokoe, Y., Bezbradica, J.S., Joyce, S., Abo, T., Iwakura, Y., Suzuki, K., Yamagoe, S.
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Journal Title
Journal of Immunology 173
Pages: 579-585
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Age-dependent variation in the proportion and number of intestinal lymphocyte subsets, especially NKT cells, double-positive CD4^+8^+ cells and B220^+T cells, in mice.2004
Author(s)
Ishimoto, Y., Tomiyama-Miyaji, C., Watanabe, H., Yokoyama, H., Ebe, K., Tsubata, S., Aoyagi, Y., Abo, T.
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Journal Title
Immunology 113
Pages: 371-377
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Increase in hepatic NKT cells in leukocyte cell-derived chemotaxin 2-deficient mice contributes to severe Concansvalin A-induced hepatitis.2004
Author(s)
Saito, T., Okumura, A., Watanabe, H., Asano, M., Ishida-Okawara, A., Sakagami, J., Sudo, K., Hatano-Yokoe, Y., Bezbradica, J.S., Joyce, S., Abo, T., Iwakura, Y., Suzuki, K., Yamagoe, S.
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Journal Title
J.Immunol 173
Pages: 579-585
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Age-dependent variation in the proportion and number of intestinal lymphocyte subsets, especially NKT cells, double-positive CD4^+8^+ cells and B220^+T cells, in mice.2004
Author(s)
Ishimoto, Y., Tomiyama-Miyaji, C., Watanabe.H., Yokoyama, H., Ebe, K., Tsubata, S., Aoyagi, Y., Abo, T.
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Journal Title
Immunology 113
Pages: 371-377
Description
「研究成果報告書概要(欧文)」より
