2022 Fiscal Year Research-status Report
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 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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| Keywords | Interleukin 27 / malaria / macrophage |
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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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| Causes of Carryover |
One of our knockout mice were not breeding well, we had to wait long time for new born mice. I need to purchase fluorescent antibodies, disposables and need to maintain conditional knockout mice for my experiments. Fluorescent-labeled
antibodies will be used for flow cytometry and immunohistochemistry, these are the fundamental assays in my research. Purified mouse cytokines for ELISA will be purchased. Other reagents and chemicals required for immunological assays and cell cultures must be purchased. Disposable laboratory tools and plastic wares will be used often in daily research assays.
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Research Products
(3 results)
