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肠蠕虫共感染增强宿主对嗜神经性黄病毒易感性
作者:小柯机器人 发布时间:2021/2/28 19:00:51

美国华盛顿大学医学院Michael S. Diamond研究团队近日取得一项新成果。他们揭示肠蠕虫共感染通过簇状细胞白细胞介素(IL)-4受体信号转导轴增强宿主对嗜神经性黄病毒的易感性。相关论文于2021年2月25日发表于《细胞》。

他们观察到肠道蠕虫Heligmosomoides polygyrus bakeri(Hpb)和West Nile病毒(WNV)共感染的小鼠死亡率增加。这种易感性增强与肠道形态和运输改变、共生细菌易位、WNV特异性T细胞反应受损以及胃肠道和中枢神经系统病毒感染增加有关。这些结果归因于2型免疫偏斜,因为Stat6-/-小鼠中的共感染可以挽救死亡率,用IL-4治疗无蠕虫WNV感染的小鼠反映了共感染,以及肠上皮细胞中的IL-4受体信号转导介导易感性表型。

此外,簇状细胞缺陷型小鼠在共同感染时显示出改善的预后,而用簇状细胞源性细胞因子IL-25或琥珀酸配体对无蠕虫小鼠的治疗会使WNV病恶化。因此,肠道中的簇状细胞-IL-4受体回路的蠕虫激活加剧了嗜神经性黄病毒的感染和疾病。

据悉,尽管肠蠕虫感染可调节对粘膜病原体的免疫力,但它们对全身微生物的作用仍未确定。

附:英文原文

Title: Enteric helminth coinfection enhances host susceptibility to neurotropic flaviviruses via a tuft cell-IL-4 receptor signaling axis

Author: Pritesh Desai, Hana Janova, James P. White, Glennys V. Reynoso, Heather D. Hickman, Megan T. Baldridge, Joseph F. Urban, Thaddeus S. Stappenbeck, Larissa B. Thackray, Michael S. Diamond

Issue&Volume: 2021-02-25

Abstract: Although enteric helminth infections modulate immunity to mucosal pathogens, theireffects on systemic microbes remain less established. Here, we observe increased mortalityin mice coinfected with the enteric helminth Heligmosomoides polygyrus bakeri (Hpb) and West Nile virus (WNV). This enhanced susceptibility is associated withaltered gut morphology and transit, translocation of commensal bacteria, impairedWNV-specific T cell responses, and increased virus infection in the gastrointestinaltract and central nervous system. These outcomes were due to type 2 immune skewing,because coinfection in Stat6/ mice rescues mortality, treatment of helminth-free WNV-infected mice with interleukin(IL)-4 mirrors coinfection, and IL-4 receptor signaling in intestinal epithelial cellsmediates the susceptibility phenotypes. Moreover, tuft cell-deficient mice show improvedoutcomes with coinfection, whereas treatment of helminth-free mice with tuft cell-derivedcytokine IL-25 or ligand succinate worsens WNV disease. Thus, helminth activationof tuft cell-IL-4-receptor circuits in the gut exacerbates infection and disease ofa neurotropic flavivirus.

DOI: 10.1016/j.cell.2021.01.051

Source: https://www.cell.com/cell/fulltext/S0092-8674(21)00094-5

期刊信息
Cell:《细胞》,创刊于1974年。隶属于细胞出版社,最新IF:36.216
官方网址:https://www.cell.com/