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

我们报道了IL-27在夏氏疟原虫（Pcc）感染的急性期产生，但在感染的慢性期负调节免疫反应。为了确定产生IL-27的细胞类型，我们产生了IL-27报告基因IL 27 p28-Venus小鼠并监测其表达。DC、巨噬细胞、单核细胞和NK细胞是Pcc感染过程中产生IL-27的主要细胞。我们假设这些细胞产生的IL-27在疟原虫感染期间的免疫应答调节中具有不同的作用。我们产生了DC或巨噬细胞中缺乏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的小鼠显示出比对照小鼠中的寄生虫血症的清除延迟。在感染的慢性期，在DC中缺乏IL-27的小鼠中，脾中响应疟疾抗原的活化的CD 4 + T细胞（CD 11 ahiCD 49 dhi）的频率和IFN-γ的产生高于对照小鼠。DC中缺乏IL-27的小鼠的疟疾特异性抗体也高于巨噬细胞中缺乏IL-27的小鼠。结果提示，DC产生的IL-27可能优先抑制Pcc感染时抗原特异性反应的发展。DC或巨噬细胞中的IL-27在抗疟原虫感染的免疫应答中发挥不同的作用。

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.