Type I interferon production elicits differential CD4+ T-cell responses in mice infected with Plasmodium berghei ANKA and P. chabaudi
Type I interferon production elicits differential CD4+ T-cell responses in mice infected with Plasmodium berghei ANKA and P. chabaudi
复制标题
I 型干扰素的产生在感染伯氏疟原虫 ANKA 和 P. chabaudi 的小鼠中引发不同的 CD4 T 细胞反应
DOI：
10.1093/intimm/dxab090
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发表时间：
2022
影响因子：
4.4
通讯作者：
K Yui.
中科院分区：
文献类型：
--
作者：
M Ntita;S-I Inoue;J-Yu Jian;G Bayarsaikhan;K Kimura;D Kimura;M Miyakoda E Nozaki;T Sakurai;D Fernandez-Ruiz;WR. Heath;K Yui.
感染人类的疟原虫具有高度多态性，可引起从无症状状态到危及生命的疾病的各种感染。然而，寄生虫之间的差异如何影响血液阶段感染期间的宿主免疫反应仍然是未知的。我们研究了感染P. bergheiANKA（PbA）或P. chabaudi chabaudiAS（Pcc），其使用识别这些寄生虫的共同表位的PbT-II细胞。在感染的急性期，PbA感染小鼠的CD 4 + T细胞反应显示出较低的参与Th 1细胞和较低比例的Ly 6Clo效应CD 4 +T细胞比PCC感染小鼠。PbT-II细胞的转录组分析表明，I型干扰素（IFN）调节的基因表达在更高的水平在Th 1和Tfh型PbT-II细胞从PbA感染的小鼠比那些从PCC感染的小鼠。此外，IFN-α水平在PbA感染的小鼠中显著高于Pc感染的小鼠。抑制I型IFN信号增加PbT-II和部分逆转的Th 1对Tfh的PbT-II细胞在PbA和PCC感染的小鼠的偏见。在记忆阶段，PbA致敏小鼠中的PbT-II细胞保持较高的数量，并表现出对抗原更好的回忆反应。然而，回忆反应没有显着不同的感染组之间的再挑战后，与PbA，这表明感染的炎症环境的影响。这些观察结果表明，在疟原虫特异性CD 4 + T细胞反应之间的差异PbA和PCC感染的小鼠与I型干扰素的生产在感染的早期阶段的差异。
AbstractPlasmodiumparasites that infect humans are highly polymorphic, and induce various infections ranging from an asymptomatic state to life-threatening diseases. However, how the differences between the parasites affect host immune responses during blood-stage infection remains largely unknown. We investigated the CD4+T-cell immune responses in mice infected withP. bergheiANKA (PbA) orP. chabaudi chabaudiAS (Pcc) using PbT-II cells, which recognize a common epitope of these parasites. In the acute phase of infection, CD4+T-cell responses in PbA-infected mice showed a lower involvement of Th1 cells and a lower proportion of Ly6Cloeffector CD4+T cells than those in Pcc-infected mice. Transcriptome analysis of PbT-II cells indicated that type I interferon (IFN)-regulated genes were expressed at higher levels in both Th1- and Tfh-type PbT-II cells from PbA-infected mice than those from Pcc-infected mice. Moreover, IFN-α levels were considerably higher in PbA-infected mice than in Pcc-infected mice. Inhibition of type I IFN signaling increased PbT-II and partially reversed the Th1 over Tfh bias of the PbT-II cells in both PbA- and Pcc-infected mice. In the memory phase, PbT-II cells in PbA-primed mice maintained higher numbers and exhibited a better recall response to the antigen. However, recall responses were not significantly different between the infection groups after re-challenge with PbA, suggesting the effect of the inflammatory environment by the infection. These observations suggest that the differences inPlasmodium-specific CD4+T-cell responses between PbA- and Pcc-infected mice were associated with the difference in type I IFN production during the early phase of the infection.