Distinct roles of IL-27 produced by macrophages and dendritic cells in shaping the immune response against Plasmodium parasites
| Project/Area Number |
20K16236
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 49040:Parasitology-related
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| Research Institution | Nagasaki University |
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Principal Investigator |
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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| Project Period (FY) |
2020-04-01 – 2024-03-31
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| Project Status |
Granted (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | Interleukin 27 / malaria / macrophage / dendritic cells |
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| Outline of Research at the Start |
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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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
2: Research has progressed on the whole more than it was originally planned.
Reason
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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| Strategy for Future Research Activity |
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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Report
(3 results)
Research Products
(3 results)
