Distinct roles of IL-27 produced by macrophages and dendritic cells in shaping the immune response against Plasmodium parasites

巨噬细胞和树突状细胞产生的 IL-27 在形成针对疟原虫寄生虫的免疫反应中的独特作用

• 批准号: 20K16236
• 负责人: バヤルサイハン ガンチメグ
• 金额: $ 2.66万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2020
• 资助国家: 日本
• 起止时间: 2020-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-20K16236/
• 关键词: Interleukin 27; malaria; macrophage; dendritic cells

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.

我们报道了IL-27在感染chabaudi疟原虫（Pcc）的急性期产生，但在感染的慢性期负向调节免疫反应。为了确定产生IL-27的细胞类型，我们制造了IL-27报告细胞IL27p28-Venus小鼠并监测其表达。巨噬细胞、单核细胞和NK细胞是Pcc感染过程中IL-27的主要产生细胞。我们假设这些细胞产生的IL-27在疟原虫感染期间的免疫反应调节中具有不同的作用。我们在dc或巨噬细胞中培养了缺乏IL-27的小鼠，并比较了这些小鼠对Pcc感染的反应。在感染的急性期，dc中缺乏IL-27的小鼠比对照组小鼠对寄生虫血症的清除延迟。在感染的慢性阶段，缺乏IL-27的dc小鼠的脾脏中CD4+ T细胞（CD11ahiCD49dhi）的激活频率和IFN-γ的产生在响应疟疾抗原时高于对照小鼠。疟疾特异性抗体在dc中缺乏IL-27的小鼠中也高于巨噬细胞中缺乏IL-27的小鼠。结果表明，dc产生的IL-27可能优先抑制Pcc感染期间抗原特异性反应的发展。巨噬细胞和DC细胞中的IL-27在抵抗疟原虫感染的免疫应答中起着不同的作用。

项目成果

Distinct roles of IL-27 produced by innate cells in shaping the immune response against Plasmodium parasite

先天细胞产生的 IL-27 在形成针对疟原虫寄生虫的免疫反应中的独特作用

• 发表时间: 2022
• 作者: Ganchimeg Bayarsaikhan;Shin-Ichi Inoue;Kazumi Kimura;Hiroki Yoshida;Masahiro Yamamoto and Katsuyuki Yui
• 通讯作者: Masahiro Yamamoto and Katsuyuki Yui

Myeloid derived interleukin-27 involvement in immune response to malaria

骨髓源性白细胞介素 27 参与疟疾免疫反应

• 发表时间: 2023
• 作者: Ganchimeg Bayarsaikhan;Shin-Ichi Inoue;Kazumi Kimura;Hiroki Yoshida;Masahiro Yamamoto and Katsuyuki Yui
• 通讯作者: Masahiro Yamamoto and Katsuyuki Yui

Interleukin-27 produced by dendritic cells involved in antigen specific response during chronic stage of plasmodium infection

树突状细胞产生的白介素 27 参与疟原虫感染慢性阶段的抗原特异性反应

• 发表时间: 2023
• 作者: Ganchimeg Bayarsaikhan;Shin-Ichi Inoue;Kazumi Kimura;Hiroki Yoshida;Masahiro Yamamoto and Katsuyuki Yui
• 通讯作者: Masahiro Yamamoto and Katsuyuki Yui