Dynamics of Host Immune Response Development During Schistosoma mansoni Infection.

Dynamics of Host Immune Response Development During Schistosoma mansoni Infection.
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DOI:
10.3389/fimmu.2022.906338
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发表时间:
2022
影响因子:
7.3
通讯作者:
--
中科院分区:
医学2区
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--
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血吸虫病是一种具有全球意义的疾病,其严重性和病理学直接关系到宿主对感染的反应。血吸虫病的免疫学叙事是通过数十年的研究建立起来的,研究人员往往专注于孤立的时间点、细胞类型和感兴趣的组织部位。然而,该领域目前缺乏对血吸虫病感染和跨多个组织部位的免疫轨迹的全面和最新的了解。我们定义了血吸虫在寄生虫生命周期的几个不同阶段,在受感染影响的三个组织部位:肝、脾和肠系膜淋巴结中引发的免疫反应。此外,通过对血吸虫感染小鼠的肝脏进行RNA-SEQ,我们对血吸虫相关肝脏病理和感染范围内的纤维化的发展产生了新的转录学见解。通过在血吸虫驱动的炎症高峰期耗尽CD11c+细胞,我们揭示了CD11c+细胞在感染期间Th2炎症的协调和调节中的关键作用。我们的数据提供了宿主免疫反应在小鼠血吸虫病过程中如何演变的最新和高分辨率的描述,强调了CD11c+细胞在指导宿主免疫病理对抗这种重要的蠕虫感染方面的重要性。
Schistosomiasis is a disease of global significance, with severity and pathology directly related to how the host responds to infection. The immunological narrative of schistosomiasis has been constructed through decades of study, with researchers often focussing on isolated time points, cell types and tissue sites of interest. However, the field currently lacks a comprehensive and up-to-date understanding of the immune trajectory of schistosomiasis over infection and across multiple tissue sites. We have defined schistosome-elicited immune responses at several distinct stages of the parasite lifecycle, in three tissue sites affected by infection: the liver, spleen, and mesenteric lymph nodes. Additionally, by performing RNA-seq on the livers of schistosome infected mice, we have generated novel transcriptomic insight into the development of schistosome-associated liver pathology and fibrosis across the breadth of infection. Through depletion of CD11c+ cells during peak stages of schistosome-driven inflammation, we have revealed a critical role for CD11c+ cells in the co-ordination and regulation of Th2 inflammation during infection. Our data provide an updated and high-resolution account of how host immune responses evolve over the course of murine schistosomiasis, underscoring the significance of CD11c+ cells in dictating host immunopathology against this important helminth infection.
DOI: 10.1007/978-1-0716-1237-8_19
发表时间: 2021
期刊: Methods in molecular biology (Clifton, N.J.)
影响因子: --
作者:
Oka A;Liu B;Herzog JW;Sartor RB
通讯作者: Sartor RB