| 研究課題/領域番号 |
20K16236
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| 研究種目 |
若手研究
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| 配分区分 | 基金 |
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| 審査区分 |
小区分49040:寄生虫学関連
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| 研究機関 | 長崎大学 |
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研究代表者 |
バヤルサイハン ガンチメグ 長崎大学, 医歯薬学総合研究科(医学系), 助教 (80841353)
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| 研究期間 (年度) |
2020-04-01 – 2024-03-31
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| 研究課題ステータス |
交付 (2022年度)
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| 配分額 *注記 |
4,160千円 (直接経費: 3,200千円、間接経費: 960千円)
2022年度: 1,560千円 (直接経費: 1,200千円、間接経費: 360千円)
2021年度: 1,300千円 (直接経費: 1,000千円、間接経費: 300千円)
2020年度: 1,300千円 (直接経費: 1,000千円、間接経費: 300千円)
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| キーワード | Interleukin 27 / malaria / macrophage / dendritic cells |
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| 研究開始時の研究の概要 |
I will examine the mechanism underlying the differential effect of IL-27 from distinct source in the development of protective immune response against Plasmodium infection. This study is critical to understand the role of innate derived cytokines for shaping adaptive immune response during malaria.
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| 研究実績の概要 |
We reported that IL-27 is produced during acute phase of the infection with Plasmodium chabaudi (Pcc) but negatively regulates the immune responses during at the chronic phase of the infection. To determine cell types that produce IL-27, we generated IL-27 reporter IL27p28-Venus mice and monitored its expression. DC, macrophage, monocytes and NK cells were the main producers of IL-27 over the course of Pcc infection. We hypothesized that IL-27 produced by these cells have differential roles in the regulation of immune responses during Plasmodium infection. We generated mice lacking IL-27 in DCs or in macrophages and compared the response of these mice to the infection with Pcc. Mice lacking IL-27 in DCs showed delay in the clearance of parasitemia than that in control mice during the acute phase of the infection. The frequencies of activated CD4+ T cells (CD11ahiCD49dhi) and IFN-γ production in the spleen in response to malaria antigen were higher in mice lacking IL-27 in DCs than those in control mice during chronic phase of the infection. Malaria specific antibodies were also higher in mice lacking IL-27 in DCs than those in mice lacking IL-27 in macrophages. The results suggest that IL-27 procduced by DCs may preferentially suppresses development of antigen specific response during infection with Pcc. IL-27 in DC or macrophages play differential roles in the immune responses against Plasmodium infection.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
2: おおむね順調に進展している
理由
We are summarizing initial findings and preparing for publication. In meantime we would like to check if IL-27 from different cells enhance secondary infection.
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| 今後の研究の推進方策 |
As stated above, we are summarizing initial results and preparing for publication. Further research will determine role of IL-27 produced by DCs or macrophages in secondary infection with plasmodium. To test this, groups of mice will be rechallenged with the heterologous parasite after complete clearance of the parasite. Mice will be monitored for parasitemia and disease progress after rechallenge. Expansion of memory cells in the spleen and their function will be checked after the rechallenge.Also we would like to check if IL-27 produced by DCs or macrophages affect on NK cell function. We will check NK cells activation and function upon infection with plasmodiun in different conditional knockout mice and compare the response.
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